Balloon coating method, balloon rotating method and balloon coating apparatus

ABSTRACT

A balloon coating method for forming a coating layer containing a water-insoluble drug on an outer surface of a balloon of a balloon catheter includes: fixing a connection portion between the balloon and an inner tube penetrating an inside of the balloon in such a manner as to clamp the connection portion by at least two clamping portions each having a groove-shaped curved surface extending along an axis of the inner tube; pulling the balloon in an axial direction of the balloon by the clamping portions to thereby straighten a bend of the balloon; and moving a dispensing tube for supplying a coating liquid containing the drug relative to the balloon in the axial direction of the balloon, while rotating the balloon about an axis of the balloon, to thereby coat the outer surface of the balloon with the coating liquid.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application claims priority to Japanese Application No. 2015-088383filed on Apr. 23, 2015, the entire content of which is incorporatedherein by reference.

TECHNICAL FIELD

The present disclosure relates to a balloon coating method, a balloonrotating method and a balloon coating apparatus for forming a coatinglayer containing a drug on a surface of a balloon.

BACKGROUND DISCUSSION

In recent years, balloon catheters have been used for improving lesionaffected areas (stenosed parts) in body lumens. A balloon catheternormally includes an elongate shaft portion, and a balloon which isprovided on the distal side of the shaft portion and is inflatable inthe radial direction. After the balloon in a deflated state is broughtto a target site in the body by way of a small body lumen, the balloonis inflated, whereby the lesion affected area can be pushed wide open.

If a lesion affected area is forcibly pushed wide open, however,excessive proliferation of smooth muscle cells may occur, causing newstenosis (restenosis). In view of this, recently, drug eluting balloons(DEBs) wherein an outer surface of a balloon is coated with a drug forrestraining stenosis have been used. The drug eluting balloon, by beinginflated, is able to instantaneously release the drug contained in thecoating on the outer surface of the balloon to the lesion affected areaand transfer the drug to the living body tissue, thereby restrainingrestenosis.

In recent years, it has been becoming clear that the morphological formof the drug in the coating on the balloon surface influences thereleasing property of the drug from the balloon surface and/or thetransferability of the drug to the tissue at the lesion affected area.For this reason, it is said that it is important to control thecrystalline form or amorphous form of the drug.

A variety of methods have been proposed for coating a balloon with adrug. For instance, U.S. Pat. No. 8,597,720 discloses a method in whicha coating solution containing a drug (therapeutic agent) is supplied toa surface of a balloon while the balloon is being rotated, and thecoating liquid is dried to form a coating layer containing the drug.

SUMMARY

The drug in the coating on the outer surface of the balloon can assumedifferent morphological forms such as crystalline form, amorphous formand mixed forms thereof, depending on various conditions such as thelength of time of volatilization of the solvent. Neither of thecrystalline form and the amorphous form is more desirable than theother, and it is desirable that the morphological form of the drug canbe selected according to the purpose.

There is a need for a balloon coating method, a balloon rotating methodand a balloon coating apparatus by which a coating liquid can be appliedto an outer surface of a balloon in an appropriate quantity, and themorphological form of the drug in the coating formed on the balloon canbe set appropriately.

According to one aspect of the present disclosure, a balloon coatingmethod for forming a coating layer containing a water-insoluble drug onan outer surface of a balloon of a balloon catheter includes: fixing aconnection portion between the balloon and an inner tube penetrating aninside of the balloon to clamp the connection portion by at least twoclamping portions each having a groove-shaped curved surface extendingalong an axis of the inner tube; pulling the balloon in an axialdirection of the balloon by the clamping portions to thereby straightena bend of the balloon; and moving a dispensing tube for supplying thecoating liquid to the balloon in the axial direction of the balloonwhile rotating the balloon about an axis of the balloon and while alsodispensing the coating liquid containing the water-insoluble drug fromthe dispensing tube to apply the coating liquid to the outer surface ofthe balloon.

According to this balloon coating method, the connection portion betweenthe inner tube and the balloon is fixed in the manner of being clampedby the clamping portions each having the groove-shaped curved surface.Therefore, the inner tube and a part of inflation of the balloon are notdamaged and can be restrained from getting eccentric, so that theposition of the outer surface of the balloon becomes less liable tofluctuate during rotation. For this reason, the coating liquid can beapplied to the outer surface of the balloon in an appropriate quantity.In addition, since the position of the outer surface of the balloon isnot liable to fluctuate during rotation, the contact force in contact ofthe dispensing tube with the balloon can be easily set to a desirablevalue, so that, for example, the morphological form of the drug in thecoating formed on the balloon can be set appropriately.

The balloon coating method may have a configuration wherein in thecoating, the balloon is rotated while pulling the balloon in the axialdirection of the balloon by the clamping portions, thereby to coat theouter surface of the balloon with the coating liquid. This configurationhelps ensure that a bend, if any, of the balloon is straightened by thetensile force, so that the position of the outer surface of the balloonbecomes less liable to fluctuate during rotation. Therefore, the coatingliquid can be applied to the outer surface of the balloon in a moreappropriate quantity. In addition, the contact force in contact of thedispensing tube with the balloon can be easily set to a desirable value,so that, for example, the morphological form of the drug in the coatingformed on the balloon can be set more appropriately. Besides, althoughthe clamping force by the clamping portions is increased because thetensile force is applied, the inner tube and the balloon can berestrained from being damaged, since the connection portion is graspedby the clamping portions each having the groove-shaped curved surface.

In the balloon coating method, the at least two clamping portions may beprovided in a collet chuck. In this case, the connection portion betweenthe inner tube and the balloon can be fixed easily and reliably by thecollet chuck, and, further, the tensile force can be effectively appliedto the balloon.

Another aspect of the present disclosure involves a balloon rotatingmethod for rotating a balloon catheter. The balloon catheter includes aballoon possessing an axis and an inner tube passing through theballoon, with the balloon possessing one end portion axially overlappingand connected in a fluid-tight manner to the inner tube at a connectionportion. The balloon rotating method comprises: clamping the connectionportion by at least two clamping portions each including a groove-shapedcurved surface extending along the axis of the inner tube; and rotatingthe balloon about the axis of the balloon while the connection portionis clamped by the clamping portions.

According to the balloon rotating method configured as above, theconnection portion between the inner tube and the balloon is pulled byfixing it in the manner of being clamped by the clamping portions eachhaving the groove-shaped curved surface. Therefore, the inner tube and apart of inflation of the balloon are not damaged and can be restrainedfrom becoming eccentric, so that the position of the outer surface ofthe balloon becomes less liable to fluctuate during rotation.

The balloon rotating method may have a configuration wherein as a partof the rotating, the balloon is rotated while pulling the balloon in anaxial direction of the balloon by the clamping portions. In this case, abend, if any, of the balloon is straightened by the tensile force, sothat the position of the outer surface of the balloon is not liable tofluctuate during rotation. In addition, although the clamping force bythe clamping portions is increased because the tensile force is applied,the inner tube and the balloon can be restrained from being damaged,since the connection portion is grasped by the clamping portions eachhaving the groove-shaped curved surface.

In the balloon rotating method, the at least two clamping portions maybe provided in a collet chuck. This helps ensure that the connectionportion between the inner tube and the balloon can be fixed easily andreliably by the collet chuck, and, further, the tensile force can beeffectively exerted on the balloon.

According to a further aspect of the present disclosure, a ballooncoating apparatus configured to form a coating layer containing awater-insoluble drug on an outer surface of a balloon of a ballooncatheter includes: at least two clamping portions configured to fix, inthe manner of clamping, a connection portion between the balloon and aninner tube penetrating an inside of the balloon, the clamping portionseach having a groove-shaped curved surface extending along an axis ofthe inner tube; a rotation driving section configured to rotate theballoon catheter; and a coating section that moves a dispensing tube forsupplying a coating liquid containing the drug relative to the balloonin an axial direction of the balloon, to thereby coat the outer surfaceof the balloon with the coating liquid.

According to the balloon coating apparatus configured as above, theconnection portion between the inner tube and the balloon can be fixedin the manner of clamping the connection portion by the clampingportions each having the groove-shaped curved surface. Therefore, theinner tube and a part of inflation of the balloon are not damaged andcan be restrained from getting eccentric, so that the position of theouter surface of the balloon becomes less liable to fluctuate duringrotation. For this reason, the coating liquid can be applied to theouter surface of the balloon in an appropriate quantity. In addition,since the position of the outer surface of the balloon is not liable tofluctuate during rotation, the contact force in contact of thedispensing tube with the balloon can be easily set to a desirable value,so that, for example, the morphological form of the drug in the coatingformed on the balloon can be set appropriately.

The balloon coating apparatus may further include a tension section thatapplies a tensile force for pulling the balloon in the axial directionof the balloon while maintaining the balloon in a rotatable state. Inthis case, a bend, if any, of the balloon can be straightened by thetensile force, so that the position of the outer surface of the balloonbecomes less liable to fluctuate during rotation. Therefore, the coatingliquid can be applied to the outer surface of the balloon in a moreappropriate quantity. In addition, the contact force in contact of thedispensing tube with the balloon can be easily set to a desirable value,so that, for example, the morphological form of the drug in the coatingformed on the balloon can be set more appropriately. Besides, althoughthe clamping force by the clamping portions is increased because thetensile force is applied, the inner tube and the balloon can berestrained from being damaged, since the connection portion is graspedby the clamping portions each having the groove-shaped curved surface.

In the balloon coating apparatus, the at least two clamping portions maybe provided in a collet chuck. In this case, the connection portionbetween the inner tube and the balloon can be fixed easily and reliablyby the collet chuck, and, further, the tensile force can be effectivelyapplied to the balloon.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic view showing an apparatus configured to carry outa balloon coating method according to a first embodiment of the presentdisclosure.

FIG. 2 is a plan view showing a balloon catheter.

FIG. 3 is a cross-sectional view showing a distal portion of the ballooncatheter.

FIGS. 4A and 4B are plan views showing a driving shaft, wherein FIG. 4Adepicts a state before the driving shaft is interlocked to a three-waycock, and FIG. 4B depicts a state after the driving shaft is interlockedto the three-way cock.

FIG. 5 is a perspective view showing a support part.

FIG. 6 is a cross-sectional view taken along the section line VI-VI ofFIG. 5.

FIG. 7 is a plan view showing a holding part.

FIG. 8 is a cross-sectional view taken along the section line VIII-VIIIof FIG. 7.

FIG. 9 is a cross-sectional view showing a state where a ballooncatheter is held by the holding portion.

FIG. 10 is a cross-sectional view showing a balloon at the time ofapplying a coating liquid to an outer surface of the balloon.

FIG. 11 is a schematic view showing an apparatus configured to carry outa balloon coating method according to a second embodiment of the presentdisclosure.

FIG. 12 is a plan view, as viewed from above, of the apparatusconfigured to carry out the balloon coating method according to thesecond embodiment.

FIG. 13 is a cross-sectional view taken along line XIII-XIII of FIG. 12.

FIG. 14 is a cross-sectional view showing a state where a lid portion isopened.

FIG. 15 is a schematic view showing a modification of the ballooncoating apparatus in the first embodiment.

DETAILED DESCRIPTION

Set forth below, with reference to the accompanying drawing figures, isa detailed description of embodiments of a balloon coating method and aballoon rotating method for forming a drug-containing coating layer on aballoon surface representing examples of the inventive balloon coatingmethod and balloon rotating method disclosed here. Dimensional ratios inthe drawings may be exaggerated for convenience of explanation and maytherefore be different from the actual ratios.

First Embodiment

A balloon coating method according to a first embodiment of the presentdisclosure is a method of forming a coating layer containing awater-insoluble drug on a surface of a balloon, and is carried out by aballoon coating apparatus 100 illustrated in FIG. 1. In the descriptionbelow, the end of a balloon catheter 10 that is inserted into a bodylumen will be referred to as the “distal end” or “distal side,” and theend at which the operator's hand operation occurs will be referred to asthe “proximal end” or “proximal side.”

First of all, the structure of the balloon catheter 10 will bedescribed. The balloon catheter 10 is a so-called rapid exchange typecatheter. As illustrated in FIGS. 2 and 3, the balloon catheter 10includes an elongate catheter shaft 20 (shaft), a balloon 30 provided ona distal portion of the catheter shaft 20, a hub 40 firmly attached(fixed) to a proximal end of the catheter shaft 20, and an anti-kinkingtube 50 provided at a joint portion between the catheter shaft 20 andthe hub 40.

The catheter shaft 20 includes a tube-shaped (tubular) proximal shaft 60whose proximal end is firmly attached (fixed) to the hub 40, atube-shaped (tubular) intermediate shaft 70 covering a distal side ordistal end of the proximal shaft 60, a tube-shaped (tubular) distalshaft 80 provided on the distal side of the intermediate shaft 70, and atube-shaped (tubular) inner tube 90 disposed inside the distal shaft 80.Inside the proximal shaft 60, the intermediate shaft 70 and the distalshaft 80 is an inflation lumen 23 through which an inflation fluid forinflating the balloon 30 flows.

The inner tube 90 includes an inner tube shaft 95 which penetrates theinside of the distal shaft 80 and the balloon 30 in a coaxial manner,and a flexible tip 96 interlocked to a distal portion of the inner tubeshaft 95. The tip 96 extends distally beyond the distal end of theballoon 30, and a distal portion of the balloon 30 is joined to an outercircumferential surface of a proximal portion of the tip 96 in aliquid-tight/fluid-tight manner. On the other hand, the proximal end ofthe inner tube shaft 95 is firmly attached (fixed) to a part in theouter circumferential direction of the intermediate shaft 70 (a sideopening formed in a side surface) in a liquid-tight/fluid-tight manner,and a proximal opening of the inner tube shaft 95 is exposed to theoutside of the intermediate shaft 70, thereby constituting a proximalopening portion 92. An inside space ranging from the distal end of theinner tube 90 to the proximal opening portion 92 constitutes a guidewire lumen 91. A guide wire is inserted in and passed through the innertube 90, while a distal opening portion 93 of the tip 96 constitutingthe inner tube 90 serves as an entrance, whereas the proximal openingportion 92 of the inner shaft 95 constituting the inner tube 90 servesas an exit. The proximal opening portion 92 may be provided in theproximal shaft 60 or the distal shaft 80, instead of the intermediateshaft 70, or may be provided at a boundary portion between theintermediate shaft 70 and the distal shaft 80.

The materials constituting the distal shaft 80, the inner tube shaft 95,the tip 96 and the intermediate shaft 70 are not particularly limited.Examples of the materials which can be preferably used include polymericmaterials such as polyolefins (e.g., polyethylene, polypropylene,polybutene, ethylene-propylene copolymer, ethylene-vinyl acetatecopolymer, ionomer, or mixtures of two or more of them), crosslinkedpolyolefins, polyvinyl chloride, polyamides, polyamide elastomers,polyesters, polyester elastomers, polyurethanes, polyurethaneelastomers, fluororesins, polyimides, and mixtures thereof.

The material constituting the proximal shaft 60 is preferably a materialwhich is comparatively high in rigidity. Examples of the material whichcan be preferably used include metals such as Ni—Ti alloys, brass, steelspecial use stainless (SUS), aluminum, etc. and resins such aspolyimides, vinyl chloride, polycarbonate, etc.

The hub 40 is provided with a hub proximal opening portion 41 thatcommunicates with the inflation lumen 23 of the catheter shaft 20 andfunctions as a port through which the inflation fluid flows in and out.The hub 40 is fixed in a liquid-tight/fluid-tight connection with theproximal shaft 60.

The anti-kinking tube 50 is disposed outside of the proximal shaft 60,in order to prevent the proximal shaft 60 from kinking near the distalend of the hub 40.

The balloon 30 is for pushing open (outwardly expanding) a stenosed partby being inflated. At a central portion in the axial direction X of theballoon 30, there is formed a cylindrical portion 31 having acylindrical shape with a constant outside diameter when inflated. Onboth sides of the cylindrical portion 31 in the axial direction X, thereare formed tapered portions 33 at which the outside diameter graduallyvaries. The cylindrical portion 31 and the tapered portions 33 on bothsides constitute a region in which the balloon 30 is actually inflated.A coating layer 32 containing a drug is formed on the whole part of anoutside surface of the cylindrical portion 31. The range of the balloon30 where the coating layer 32 is formed is not limited only to thecylindrical portion 31 but may include at least part of the taperedportions 33 in addition to the cylindrical portion 31; alternatively,the coating layer 32 may be formed on only part of the cylindricalportion 31.

A portion of the balloon 30 on the distal side of the distal-sidetapered portion 33 constitutes a distal joint portion 34 (distal jointportion or distal joined region) that is joined, by adhesion or fusionbonding, to an outer circumferential surface of the tip 96 constitutingthe inner tube 90, in a liquid-tight/fluid-tight manner. A portion ofthe balloon 30 on the proximal side of the proximal-side tapered portion33 constitutes a proximal joint portion 35 (proximal joined region) thatis joined, by adhesion or fusion bonding, to an outer circumferentialsurface of a distal portion of the distal shaft 80 in aliquid-tight/fluid-tight manner. The inside of the balloon 30communicates with the inflation lumen 23 formed in the catheter shaft20, and the inflation fluid can flow into the balloon 30 from theproximal side through the inflation lumen 23. The balloon 30 is inflatedwhen the inflation fluid flows into the balloon 30, and is brought intoa folded state when the inflation fluid having flowed into the balloonis subsequently discharged from the balloon. The part to which a distalportion of the balloon 30 is joined may not necessarily be the tip 96 ofthe inner tube 90 but may be the inner tube shaft 95. In addition, theinner tube may be composed only of the inner tube shaft, without the tipbeing provided.

The balloon 30 preferably has a certain degree of flexibility and acertain degree of hardness such that the balloon 30, upon reaching ablood vessel or tissue or the like, can be inflated and can release thedrug from the coating layer 32 provided on its surface. Specifically,the balloon 30 is formed from a metal or a resin, and at least the outersurface of the balloon 30 on which to provide the coating layer 32 ispreferably formed of a resin. Examples of the material which can be usedto constitute at least the surface of the balloon 30 include polyolefinssuch as polyethylene, polypropylene, polybutene, ethylene-propylenecopolymer, ethylene-vinyl acetate copolymer, ionomer or mixtures of twoor more of them, thermoplastic resins such as flexible polyvinylchloride resin, polyamides, polyamide elastomers, polyesters, polyesterelastomers, polyurethanes, fluororesins, etc., silicone rubbers, latexrubber, and so on. Among these, preferred are polyamides. Specifically,at least part of the surface of the inflatable portion of the medicaldevice to be coated with the drug is formed of a polyamide. The surfaceof the inflatable portion formed of a polyamide provides a smoothsurface. The polyamide is not particularly limited so long as it is apolymer having an amide bond. Examples of the polyamide includehomopolymers such as polytetramethylene adipamide (nylon 46),polycaprolactam (nylon 6), polyhexamethylene adipamide (nylon 66),polyhexamethylene sebacamide (nylon 610), polyhexamethylene dodecamide(nylon 612), polyundecanolactam (nylon 11), polydodecanolactam (nylon12), etc., copolymers such as caprolactam/lauryllactam copolymer (nylon6/12), caprolactam/aminoundecanoic acid copolymer (nylon 6/11),caprolactam/ω-aminononanoic acid copolymer (nylon 6/9),caprolactam/hexamethylenediammonium adipate copolymer (nylon 6/66),etc., and aromatic polyamides such as copolymer of adipic acid andmetaxylenediamine, copolymer of hexamethylene diamine and m,p-phthalicacid, etc. Further, polyamide elastomers which are block copolymersincluding nylon 6, nylon 66, nylon 11, nylon 12 or the like as hardsegment and polyalkylene glycol, polyether, aliphatic polyester or thelike as soft segment may also be used as a base material for the medicaldevice according to the present embodiment. The above-mentionedpolyamides may be used either singly or in a combination of two or moreof them.

The balloon 30 is formed with the coating layer 32 either directly onthe outer surface of the balloon or with a pretreatment layer such as aprimer layer formed between the outer surface of the balloon and thecoating layer 32, depending on a coating method which will be describedlater.

Next, the balloon coating apparatus 100 will be described. Asillustrated in FIG. 1, the balloon coating apparatus 100 includes arotation driving section 110 (first rotation driving section) configuredto rotate the balloon 30 about the axis X of the balloon 30, a basesection 120 configured to support the balloon catheter 10, and a coatingsection 130 provided with a dispensing tube 134 for dispensing a coatingliquid and applying the coating liquid to an outer surface of theballoon 30. Further, the balloon coating apparatus 100 includes arectilinear moving section 140 configured to move the dispensing tube134 relative to the balloon 30, a tension section 150 (second rotationdriving section) configured to apply a tensile force to the balloon 30,and a control unit 160 configured to control the balloon coatingapparatus 100.

As shown in FIGS. 1, 4A and 4B, the rotation driving section 110includes a driving shaft 111 inserted into a three-way cock 170 attachedto the hub proximal opening portion 41 (see FIG. 2) of the hub 40 of theballoon catheter 10, a first motor 112 for rotating the driving shaft111, and a first shaft joint 114 interlocking a rotary shaft 115 of thefirst motor 112 with the driving shaft 111. With the three-way cock 170attached to the hub 40, it is possible to introduce the inflation fluidinto the balloon 30 to inflate the balloon 30, by opening the three-waycock 170, and to maintain the inflated state of the balloon 30 byclosing the three-way cock 170.

The first motor 112 is fixed to a bed 121. The driving shaft 111 isinterlocked to the rotary shaft 115 of the first motor 112 by the firstshaft joint 114, and is formed at a distal portion thereof with a maleluer taper (projected luer taper) 116 the diameter of which decreasesdistally. The male luer taper 116 can be inserted into a female luertaper (recessed luer taper) 171 formed in the three-way cock 170, to befitted to the female luer taper 171 with a frictional force. The taperratio of the male luer taper 116 and the female luer taper 171 isprescribed in International Organization for Standardization (ISO) 594and Japanese Industrial Standards (JIS) (commentary on standards andreference concerning medical devices), and is prescribed to be 6%. Therange of insertion of the driving shaft 111 is within the range of thethree-way cock 170, and the driving shaft 111 can be fitted to anddetached from the three-way cock 170 easily, which is highly userfriendly.

The male luer taper 116 of the driving shaft 111 may be fitted to afemale luer taper which is formed not in the three-way cock 170 but atthe hub proximal opening portion 41 of the hub 40. In this case, thedriving shaft 111 is not inserted to the distal side beyond the hub 40.Since the driving shaft 111 is not inserted to the distal side beyondthe hub 40, the catheter shaft 20 can bend flexibly, and the drivingshaft 111 can be fitted to and detached from the balloon catheter 10easily, which is highly user friendly.

The base section 120 includes the bed 121 serving as a base, and asupport part 180 fixed to the bed 121 and supporting the catheter shaft20 such that the catheter shaft 20 is rotatable. The base section 120includes a guide groove part (guide groove) 122 holding the tensionsection 150 such that the tension section 150 can be movedrectilinearly, and a rack 123 having teeth aligned rectilinearly.

As shown in FIGS. 1, 5 and 6, the support part 180 includes a supportbase 181 formed with a groove portion (groove) 182 in which the cathetershaft 20 is rotatably accommodated, a lid portion (lid) 183 configuredto cover a support surface 186 formed with the groove portion 182 of thesupport base 181, and hinge portions 184 connecting the lid portion 183to the support base 181 such that the lid portion 183 can be opened andclosed in relation to the support base 181. The lid portion 183 isprovided with a handle 185 for easy grasping at the times of opening andclosing the lid portion 183.

The support base 181 is formed to be elongate along the axial directionX such as to be able to support the elongate catheter shaft 20. Thegroove portion 182 formed in the support surface 186 includes a firstgroove portion 182A configured to support a part of the catheter shaft20 that is near the balloon 30, a second groove portion 182B configuredto support a range inclusive of a part of the catheter shaft 20 that isnear the proximal opening portion 92, and a third groove portion 182Cconfigured to support a portion of the catheter shaft 20 that is on theproximal side of the proximal opening portion 92. The first grooveportion 182A, the second groove portion 182B and the third grooveportion 182C are arranged on an extension line of the driving shaft 111,aligned in this order from the distal side. The first groove portion182A, the second groove portion 182B and the third groove portion 182Cmay be located with a slight deviation to the vertically lower side fromthe extension line of the driving shaft 111, taking into account bendingof the catheter shaft 20 due to its own weight between the driving shaft111 and the support base 181. The second groove portion 182B is greaterin width and depth than the first groove portion 181A and the thirdgroove portion 182C, such that a part of the catheter shaft 20 near theproximal opening portion 92 that is locally projecting from thesurroundings can be restrained from being damaged by friction. Thegroove portion formed in the support base 181 may be constant in widthand depth. In addition, the groove portion formed in the support base181 may be constant, or varies from part to part, in only one of widthand depth.

The width and depth of the groove portion 182 (the first groove portion182A, the second groove portion 182B and the third groove portion 182C)are preferably greater than the outside diameter of the catheter shaft20 by approximately 1 mm to 5 mm. If the width and depth of the grooveportion 182 are too small, the catheter shaft 20 is liable to be damagedby friction, and the load on rotation becomes large, making rotation ofthe balloon 30 unstable; as a result, it may be difficult to form thecoating layer 32 in an appropriate amount, and it may be difficult tocontrol, for example, the morphological form of the drug in the coatinglayer 32. On the other hand, if the width and depth of the grooveportion 182 are too large, the catheter shaft 20 moves irregularlywithin the groove portion 182 upon rotation, making the rotation of theballoon 30 unstable; consequently, it may be difficult to form thecoating layer 32 in an appropriate amount, and it may be difficult tocontrol, for example, the morphological form of the drug in the coatinglayer 32.

The shape of the groove portion 182 has a semicircular shape at a bottomsurface in cross-section orthogonal to the axial direction X in thisembodiment, but this is not restrictive, and the shape may be a V shapeor a tetragonal shape, for example. The shape of the groove portion 182is preferably such as to make surface contact with the catheter shaft20, such that the catheter shaft 20 is not liable to be damaged.Therefore, the shape of the groove portion 182 preferably does not havea projecting part, such as a W-shaped part, in cross-section orthogonalto the axial direction X.

The lid portion 183 is rotatably held on the support base 181 by thehinge portions 184, can cover the support surface 186 to close thegroove portion 182, and can be separated from the support surface 186 toexpose the groove portion 182. The lid portion 183 functions to maintainthe catheter shaft 20, which is rotated in the groove portion 182,within the groove portion 182. The lid portion 183 preferably has acertain degree of weight such that the rotating catheter shaft 20 wouldnot fly out of the groove portion 182, the weight being, for example,not less than 30 g. The lid portion 183 may be provided with a lockingmechanism (not shown) for fixing the lid portion 183 to the support base181. The locking mechanism may be, for example, snap fit.

The materials constituting the support base 181 and the lid portion 183are not specifically restricted, and there can be used those materialswhich have a low coefficient of friction, such as PTFE(polytetrafluoroethylene) and rigid polyethylene.

As shown in FIG. 1, the tension section 150 (second rotation drivingsection) includes a sliding part 151 fitted to the guide groove part 122of the base section 120, a pinion 152 meshed with the rack 123, a dial153 for rotating the pinion 152, and a holding part 190 configured tohold the balloon catheter 10. Further, the tension section 150 includesa second motor 154 for rotating the holding part 190, and a second shaftjoint 156 interlocking a rotary shaft 155 of the second motor 154 withthe holding part 190.

The sliding part 151 is slidably fitted to the guide groove part 122 ofthe base section 120, and slides within the guide groove part 122,thereby moving the second motor 154 rectilinearly. The pinion 152 isrotated by rotational operation of the dial 153, and, by meshing withthe rack 123, can move the sliding part 151 along the guide groove part122. With the dial 153 rotated, a tensile force can be exerted on theballoon 30. The tensile force, which is not particularly limited, ispreferably 5 N to 15 N, for example. If the tensile force is too small,bend of the balloon 30 cannot be straightened. If the tensile force istoo large, on the other hand, the balloon 30 may be damaged by thetensile force. When the tensile force is exerted on the balloon 30, aforce acts in such a direction as to disengage the male luer taper 116of the driving shaft 111 from the female luer taper 171 of the three-waycock 170. Therefore, a fixing strength between the driving shaft 111 andthe three-way cock 170 is desirably at such a level as to be able toendure the tensile force exerted, and is, for example, 10 N to 50 N. Ifthe fixing strength between the driving shaft 111 and the three-way cock170 is too strong, the hub 40 may be damaged when the balloon catheter10 is detached from the apparatus. For instance, in the case of aballoon catheter 10 wherein the balloon 30 is formed of a polyamideresin, the outside diameter of the balloon 30 when inflated is 6 mm andthe length of the balloon 30 is 150 mm, it has been confirmed thatexertion of a force of 25 N damages the balloon 30. If the fixingstrength between the driving shaft 111 and the three-way cock 170 is tooweak, on the other hand, exertion of the tensile force on the balloon 30may cause the driving shaft 111 and the three-way cock 170 to bedisengaged from each other.

Instead of manual rotation of the dial 153, a motor or the like may beprovided and controlled.

As shown in FIGS. 7 and 8, the holding part 190 includes a collet chuck191, and a chuck holder 200 for holding the collet chuck 191.

The collet chuck 191 is formed therein with slits 195 such that aplurality of (in this embodiment, four) clamping portions 193 havingclamping surfaces 194 shaped correspondingly to the shape of an objectto be grasped are arranged in the circumferential direction of thecollet chuck 191. The collet chuck 191 is formed with a tapered surface196 at an outer circumferential surface on an end portion side where theclamping portions 193 are formed, and is formed, on the opposite sidefrom the side where the clamping portions 193 are formed, with ainterlock portion 197 configured to interlock with the second shaftjoint 156. The interlock portion 197 is smaller in outside diameter thanthe clamping portions 193. Between the clamping portions 193 and theinterlock portion 197 is formed a stepped portion 198 where outsidediameter is reduced. The clamping surfaces 194 are formed ofgroove-shaped curved surfaces extending along the axis of the distaljoint portion 34 between the balloon 30 and the inner tube 90, the jointportion 34 being grasped. The clamping surfaces 194 can clamp a portionof the side surface of the distal joint portion 34, such thatdeformation of the distal joint portion 34 is prevented as securely aspossible. A scroll chuck, a drill chuck or an independent chuck may beused in place of the collet chuck 191, so long as the distal jointportion 34 can be clamped on a surface basis such that deformation ofthe distal joint portion 34 is prevented as securely as possible. Inaddition, the number of the clamping portions is not limited to four, solong as the number is not less than two.

The chuck holder 200 includes a first holder 201 that the interlockportion 197 of the collet chuck 191 penetrates, and a second holder 202that the clamping portions 193 of the collet chuck 191 contact. Thefirst holder 201 is a tube-shaped member that the interlock portion 197of the collet chuck 191 penetrates. The first holder 201 is formed onone end side with an attachment portion 203 configured to make contactwith the stepped portion 198 of the collet chuck 191 such that thestepped portion 198 is caught on the attachment portion 203, and isformed with a first screw portion 205 at an outer circumferentialsurface of the attachment portion 203. The second holder 202 is atube-shaped member having a second screw portion 206 for screwengagement with the first screw portion 205, and is formed at an innercircumferential surface of the second holder 202 with a tapered push-insurface 204 for contact with the tapered surface 196 of the collet chuck191. When the collet chuck 191 is disposed inside the first holder 201to cause the attachment portion 203 to contact the stepped portion 198,the second screw portion 206 of the second holder 202 is put into screwengagement with the first screw portion 205 of the first holder 201 andthe second holder 202 is rotated, whereby the second holder 202 is movedcloser to the first holder 201. When the second holder 202 is movedcloser to the first holder 201, the push-in surface 204 of the secondholder 202 slides on the tapered surface 196 of the collet chuck 191,and the clamping portions 193 are deformed such that the slits 195 arenarrowed, so that the clamping surfaces 194 come closer to one another.As a result, a distal portion of the balloon catheter 10 is clamped atthe center of the clamping surfaces 194. The part to be clamped by theclamping portions 193 is preferably the distal joint portion 34 wherethe balloon 30 and the inner tube 90 of the balloon catheter 10 arejoined together, but this is not restrictive, and other parts may beclamped so long as the other parts can be clamped.

Examples of materials which can be used to constitute the collet chuck191 and the chuck holder 200 include metals such as stainless steel,aluminum, etc. and resins such as fluororesins,acrylonitrile-butadiene-styrene resin, polyethylene, etc.

At the time of grasping the balloon catheter 10 by the collet chuck 191,a core member 207 is disposed in the guide wire lumen 91, as shown inFIGS. 3 and 9, in such a manner as to prevent the balloon catheter 10from being crushed. The distal portion of the core member 207 protrudesdistally beyond the distal opening portion 93 of the guide wire lumen91, and has its proximal portion located on the proximal side of aregion of inflation of the balloon 30. The protrusion length L1 of thecore member 207 from the distal opening portion 93 is not particularlylimited, but is preferably such a length that the core member 207 can bereliably protruded enough to restrain the balloon catheter 10 fromcrushing, and is, for example, 2 mm to 50 mm.

Since the distal portion of the core member 207 protrudes distallybeyond the distal opening portion 93 of the guide wire lumen 91 and theproximal portion of the core member 207 is located on the proximal sideof the region of inflation of the balloon 30, the core member 207 ispresent inside the part to be clamped by the clamping portions 193,whereby deformation of the balloon catheter 10 due to crushing isrestrained.

The proximal portion of the core member 207 does not protrude proximallyfrom the proximal opening portion 92 of the guide wire lumen 91, but islocated near the proximal opening portion 92 or on the distal side ofthe proximal opening portion 92. The position of the proximal portion ofthe core member 207 is at the proximal end of the balloon inflation part(balloon fusion-bonded part 35) or on the proximal side of the proximalend of the balloon inflation part (balloon fusion-bonded part 35). Theproximal portion of the core member 207 is preferably in proximity tothe proximal opening portion 92. The separated distance L2 (FIG. 3) bywhich the proximal portion of the core member 207 is separated distallyfrom the proximal opening portion 92 is not particularly limited, andis, for example, 0 mm to 50 mm. The proximal portion of the core member207 may be located near the proximal opening portion 92, so long as theproximal portion of the core member 207 does not protrude proximallyfrom the proximal opening portion 92. Since the proximal portion of thecore member 207 does not protrude proximally from the proximal openingportion 92, the core member 207 can, even upon rotation of the ballooncatheter 10, be restrained from interfering with external members, and,accordingly, it can be ensured that the position of the outer surface ofthe balloon 30 is not liable to fluctuate during rotation.

When crushing of the balloon catheter 10 is restrained and the positionof the outer surface of the balloon 30 is not liable to fluctuate duringrotation, it becomes possible to apply a coating liquid to the outersurface of the balloon 30 in a more appropriate quantity. Further, whenthe position of the outer surface of the balloon 30 is not liable tofluctuate during rotation, it becomes relatively easy to set the contactforce in contact of the dispensing tube 134 with the balloon 30 to adesirable value, and it becomes possible to appropriately set, forexample, the morphological form of the drug in the coating formed on theballoon 30.

A value obtained by subtracting the outside diameter of the core member207 from the inside diameter of the guide wire lumen 91 is preferablygreater than 0 and not greater than 0.5 mm. If the outside diameter ofthe core member 207 is too large in relation to the inside diameter ofthe guide wire lumen 91, the inner tube 90 in which the guide wire lumen91 is formed is liable to be damaged by the core member 207. If theoutside diameter of the core member 207 is too small in relation to theinside diameter of the guide wire lumen 91, the inner tube 90 is liableto be deformed when the inner tube 90 is clamped by the clampingportions 193.

Because the balloon catheter 10 according to this embodiment is a rapidexchange type balloon catheter, the guide wire lumen 91 does not rangeor extend to the hub 40, and the core member 207 is not present in thehub 40.

As shown in FIG. 1, the rectilinear moving section 140 includes amovable base 141 movable rectilinearly in a direction parallel to theaxis X of the balloon 30, and a tube positioning part 142 which isdisposed on the movable base 141 and is configured to move thedispensing tube 134 in a Y-axis direction and a Z-axis direction (seeFIG. 10) which are orthogonal to the axis X. The movable base 141 ismovable rectilinearly by a drive source, such as a motor, incorporatedtherein. The coating section 130 is mounted on the movable base 141, andthe movable base 141 moves the coating section 130 rectilinearly in bothdirections along the axis X of the balloon catheter 10. The tubepositioning part 142 includes a tube fixing portion 143 to which thedispensing tube 134 is fixed, and a driving portion 144 configured tomove the tube fixing portion 143 in the Y-axis direction and the Z-axisdirection. The driving portion 144 has a two-axis slider structurecapable of movement by a drive source, such as a motor or a cylinder,incorporated therein, whereby the driving portion 144 can move the tubefixing portion 143 in both the Y-axis direction and the Z-axisdirection. The Y-axis direction and the Z-axis direction in which thedispensing tube 134 is moved in a plane orthogonal to the axis X of theballoon catheter 10 may not necessarily be defined as the verticaldirection and a horizontal direction.

The coating section 130 includes a vessel 131 for containing the coatingliquid, a liquid feed pump 132 for feeding the coating liquid in anarbitrary feeding quantity, and the dispensing tube 134 for applying thecoating liquid to the balloon 30.

The liquid feed pump 132 is, for example, a syringe pump. Under controlof the control unit 160, the liquid feed pump 132 can suck the coatingliquid from the vessel 131 through a suction tube 133, and can supplythe coating liquid into the dispensing tube 134 through a supply tube135 in an arbitrary feeding quantity. The liquid feed pump 132 isdisposed on the movable base 141, and can be moved rectilinearly by themovement of the movable base 141. The liquid feed pump 132 is notrestricted to the syringe pump so long as it can feed the coatingliquid, and may be, for example, a tube pump.

The dispensing tube 134 is a member which communicates with the supplytube 135 and by which the coating liquid supplied from the liquid feedpump 132 through the supply tube 135 is ejected onto the outer surfaceof the balloon 30. The dispensing tube 134 is a circular tube-shapedmember which is flexible. The dispensing tube 134 has its upper endfixed to the tube fixing portion 143, extends vertically downward fromthe tube fixing portion 143, and is formed with an opening at anejection end 136 which is its lower end. The opening formed at theejection end 136 is substantially perpendicularly to the axis of thedispensing tube 134. By moving the movable base 141, the dispensing tube134 can be moved rectilinearly in both directions along the axialdirection X of the balloon catheter 10, together with the liquid feedpump 132 disposed on the movable base 141. In addition, as shown in FIG.10, the dispensing tube 134 can be moved by the driving portion 144 intwo different directions (in this embodiment, the Y-axis direction whichis the vertical direction and the Z-axis direction which is thehorizontal direction) in a plane orthogonal to the axial direction X. Apart of a side surface on an end portion side of the dispensing tube 134(the part of a continuous length in the extending direction of thedispensing tube 134) is disposed in such a manner as to contact theouter surface of the balloon 30. The dispensing tube 134 can supply thecoating liquid to the outer surface of the balloon 30, in the state ofbeing pressed against the balloon 30 and being bent. Alternatively, aportion on the distal end portion side of the dispensing tube 134 may bepreshaped to possess a bent shape (permanent bent shape) before anycontact with the balloon to form a certain angle relative to thelongitudinal axis of the dispensing tube 134, and a side surface of thedistal end of the dispensing tube 134 thus bent or at least part of theside surface may be disposed to contact the outer surface of the balloon30.

The dispensing tube 134 may not necessarily be circular tube-like inshape, so long as the dispensing tube 134 can supply the coating liquid.And the dispensing tube 134 may not necessarily extend in the verticaldirection, so long as the dispensing tube 134 can eject the coatingliquid.

The dispensing tube 134 is preferably formed of a flexible material,such that the contact load in contact with the balloon 30 can be reducedand the change of the contact position attendant on rotation of theballoon 30 can be absorbed by bending. Examples of the material whichcan be used to constitute the dispensing tube 134 include polyolefinssuch as polyethylene, polypropylene, etc., cyclic polyolefins,polyesters, polyamides, polyurethanes, and fluororesins such as PTFE(polytetrafluoroethylene), ETFE (tetrafluoroethylene-ethylenecopolymer), PFA (tetrafluoroethylene-perfluoroalkylvinyl ethercopolymer), FEP (tetrafluoroethylene-hexafluoropropylene copolymer),etc., but the material is not specifically restricted so long as thematerial is flexible and deformable.

The outside diameter of the dispensing tube 134 is not particularlylimited, and is, for example, 0.1 mm to 5.0 mm, preferably 0.15 mm to3.0 mm, and more preferably 0.3 mm to 2.5 mm. The inside diameter of thedispensing tube 134 is not specifically restricted, and is, for example,0.05 mm to 3.0 mm, preferably 0.1 mm to 2.0 mm, and more preferably 0.15mm to 1.5 mm. The length of the dispensing tube 134 is not particularlylimited, and is preferably a length of up to 5 times the diameter of theballoon; specifically, the length is, for example, 1.0 mm to 50 mm,preferably 3 mm to 40 mm, and more preferably 5 mm to 35 mm.

The control unit 160 is composed, for example, of a computer, andgenerally controls the rotation driving section 110, the rectilinearmoving section 140, the tension section 150 and the coating section 130.The control unit 160 can cause the first motor 112 of the rotationdriving section 110 and the second motor 154 of the tension section 150to rotate synchronously at the same rotational speed. In addition, thecontrol unit 160 can generally control the rotational speed of theballoon 30, initial positioning of the dispensing tube 134 relative tothe balloon 30, the moving speed of the dispensing tube 134 in the axialdirection X relative to the balloon 30, the ejection rate of the drugfrom the dispensing tube 134, and the like.

The coating liquid contains a water-insoluble drug and a solvent. Afterthe coating liquid is supplied to the outer surface of the balloon 30,the solvent is volatilized, whereby a coating layer 32 having acrystalline layer or an amorphous layer is formed on the outer surfaceof the balloon 30. The balloon 30 and the coating layer 32 can be usedas a drug eluting balloon for gradually eluting the drug in a livingbody.

The water-insoluble drug herein means a drug which is insoluble ordifficultly soluble in water; specifically, the solubility of thewater-insoluble drug in water is less than 5 mg/mL at pH 5 to 8. Thesolubility may be less than 1 mg/mL, or, further, less than 0.1 mg/mL.The water-insoluble drug includes fat-soluble drug.

Some examples of the preferred water-insoluble drug includeimmunosuppressant, for example, cyclosporines inclusive of cyclosporine,immunoadjuvant such as rapamycin, etc., carcinostatic agent such aspaclitaxel, etc., antiviral or antibacterial agent, antineoplasticagent, analgesic agent, anti-inflammatory agent, antibiotic,antiepileptic, anxiolytic agent, antiparalytic agent, antagonist, neuronblocking agent, anticholinergic agent, cholinergic agent, muscarineantagonist, muscarinic agent, antiadrenergic agent, antiarrhythmicagent, antihypertensive agent, hormone preparation, and nutritionalsupplement.

The water-insoluble drug is preferably at least one selected fromrapamycin, paclitaxel, docetaxel, and everolimus. The rapamycin,paclitaxel, docetaxel and everolimus herein include their analogs and/orderivatives so long as the analogs and/or derivatives have equivalentdrug activity to the original. For example, paclitaxel and docetaxel arein an analog relation. Rapamycin and everolimus are in a derivativerelation. Among these, more preferable is paclitaxel.

The water-insoluble drug may further contain an excipient. The excipientis not particularly restricted so long as it is pharmaceuticallyacceptable. Examples of the excipient include water-soluble polymer,sugar, contrast agent, citric acid ester, amino acid ester, glycerolester of short-chain monocarboxylic acid, and salts and surfactants thatare pharmaceutically acceptable.

The excipient is preferably small in amount based on the water-insolubledrug, and preferably does not form a matrix. The excipient preferablydoes not contain, but may contain, micelle, liposome, contrast agent,emulsifier or surfactant. Further, the excipient preferably does notcontain polymer but contains only low molecular compounds.

The solvent is not particularly limited. Examples of the solvent includetetrahydrofuran, ethanol, glycerin (also called glycerol orpropane-1,2,3-triol), acetone, methanol, dichloromethane, hexane, ethylacetate and water. Among these, preferred are mixed solvents of some oftetrahydrofuran, ethanol, acetone and water.

Now, a balloon coating method for forming a coating layer 32 containingthe water-insoluble drug on a surface of the balloon 30 by use of theaforementioned balloon coating apparatus 100 will be described below.

First, the three-way cock 170 is interlocked to the hub proximal openingportion 41 of the hub 40 of the balloon catheter 10, an inflation fluidis caused to flow into the balloon 30 by opening the three-way cock 170and using a syringe or the like, to thereby inflate the balloon 30, andafter the balloon is inflated, the three-way cock 170 is closed tomaintain the inflated state of the balloon 30. A coating layer 32 canalso be formed on the surface of the balloon 30 without inflating theballoon 30, and, in that case, it is unnecessary to supply the inflationfluid into the balloon 30.

Next, the lid portion 183 of the support base 181 is opened, thecatheter shaft 20 is accommodated in the groove portion 182, and the lidportion 183 is closed. The shaft 20 is accommodated in the grooveportion 182 while the core member 207 is positioned in the guide wirelumen 91. The proximal opening portion 92 of the catheter shaft 20 isaccommodated in the second groove portion 182B, which is greater thanthe first groove portion 182A and the third groove portion 182C in widthand depth.

Subsequently, the male luer taper 116 of the driving shaft 111 isinserted into and interlocked to the female luer taper 171 of thethree-way cock 170. This results in that a rotating force can be appliedto the proximal portion of the balloon catheter 10 from the first motor112.

Next, in the condition where the clamping portions 193 of the colletchuck 191 are opened wider than the distal joint portion 34 of theballoon catheter 10, the distal joint portion 34 of the balloon catheter10 is inserted into the inside of the clamping portions 193. Thereafter,the second holder 202 is rotated relative to the first holder 201,whereon the second holder 202 is moved closer to the first holder 201,the push-in surface 204 of the second holder 202 slides on the taperedsurface 196 of the collet chuck 191, and the clamping portions 193 aredeformed in such a manner as to move toward the center. This results inthat the clamping surfaces 194 come closer to one another, and thedistal joint portion 34 of the balloon catheter 10 is clamped by theclamping surfaces 194. Consequently, it becomes possible to apply arotating force to the distal portion of the balloon catheter 10 from thesecond motor 154.

The order in which the balloon catheter 10 is disposed on the drivingshaft 111, the collet chuck 191 and the support base 181 is notparticularly limited.

Subsequently, the dial 153 is rotated to move the second motor 154 andthe collet chuck 191 distally, whereon a tensile force acts on theballoon 30, whereby bend of the balloon 30 is straightened.

Next, the dispensing tube 134 is positioned relative to the balloon 30.First, the position of the movable base 141 is adjusted, to performpositioning of the dispensing tube 134 with respect to the X-axisdirection. In this instance, the dispensing tube 134 is positioned sothat the dispensing tube 134 is located on the distalmost side of aregion where the coating layer 32 is formed on the balloon 30.

Subsequently, the driving portion 144 is operated to move the dispensingtube 134, such that the dispensing tube 134 contacts the balloon 30, asshown in FIG. 10. At the position where the dispensing tube 134 contactsthe balloon 30, the balloon 30 is rotated in a direction reverse to theejection direction in which the coating liquid is ejected from thedispensing tube 134. Thus, in FIG. 10, the ejection direction in whichthe coating liquid is ejected from the dispensing tube 134 isdownward/clockwise, while the balloon 30 is rotated in thecounter-clockwise direction.

The dispensing tube 134 approaches the outer surface of the balloon 30,and contacts the balloon 30 while bending by being pressed against theballoon 30 or without bending due to such pressing. In this instance, aside surface on the end portion side of the dispensing tube 134 isconfigured to contact the surface of the balloon 30, by so arranging thecomponents.

Next, the coating liquid is supplied to the dispensing tube 134 whilecontrolling the liquid feed amount by the liquid feed pump 132, and theballoon catheter 10 is rotated by exerting driving forces on both adistal portion and a proximal portion of the balloon catheter 10 by thefirst motor 112 and the second motor 154. That is, the one motor 112exerts a driving force on the proximal portion of the balloon catheter10 to rotate the balloon catheter 10 in one direction and the othermotor 154 exerts a driving force on the distal portion of the ballooncatheter 10 to rotate the balloon catheter 10 in the same direction,thus rotating the balloon catheter 10 in the one direction. Then, themovable base 141 is moved to gradually move the dispensing tube 134proximally along the X-direction. Since the dispensing tube 134 is movedrelative to the balloon 30, the coating liquid ejected from the openingportion of the dispensing tube 134 is applied to the outercircumferential surface of the balloon 30 while drawing a spiral. Thatis, the coating liquid is applied to the outer peripheral surface of theballoon 30 in a spiral fashion. In this case, after the outer surface ofthe balloon 30 is coated with the coating liquid at a position rotatedin the direction (in this embodiment, upward direction in FIG. 10)reverse to the ejection direction of the coating liquid of thedispensing tube 134 (reverse to the extending direction of thedispensing tube 134) so as to complete forming a morphological form ofcrystals of the water-insoluble drug, the part coated with the coatingliquid does not contact other member (for example, a dispensing tube 134whose extending direction coincides with or is reverse to the rotatingdirection). In this coating method in which the direction ofejection/coating is reverse to the direction of rotation, the dispensingtube contacts and traces the part coated with the coating solutionaround a position on a circumference of a balloon during coating.Tracing the wet part with a dispending tube helps generate crystalcores. Since the part coated with the coating liquid does not contact,for example, a dispensing tube 134 whose extending direction (directionof ejection of the coating liquid) coincides with the rotatingdirection, it is possible to eliminate the possibility of hampering theformation of “a morphological form wherein crystals of thewater-insoluble drug include a plurality of elongate bodies havingindependent long axes,” and it is possible to preclude the possibilityof breakage of the morphological form after the formation.

The moving speed of the dispensing tube 134 is not particularly limited,and is, for example, 0.01 mm/second to 2 mm/second, preferably 0.03mm/second to 1.5 mm/second, and more preferably 0.05 mm/second to 1.0mm/second. The ejection rate of the coating liquid from the dispensingtube 134 is not specifically restricted, and is, for example, 0.01μL/second to 1.5 μL/second, preferably 0.01 μL/second to 1.0 μL/second,and more preferably 0.03 μL/second to 0.8 μL/second. The rotationalspeed of the balloon 30 is not particularly limited, and is, forexample, 10 rpm to 300 rpm, preferably 30 rpm to 250 rpm, and morepreferably 50 rpm to 200 rpm. The first motor 112 and the second motor154 can be synchronously rotated within these ranges of rotationalspeed. The diameter of the balloon 30 at the time of coating the balloon30 with the coating liquid is not specifically restricted, and is, forexample, 1 mm to 10 mm, preferably 2 mm to 7 mm.

When the balloon catheter 10 is rotated, a balloon main body portion isrotated within the groove portion 182 of the support base 181. In thiscase, since the proximal opening portion 92 partially projecting fromthe surroundings, of the catheter shaft 20, is accommodated in thesecond groove portion 182B formed to be larger than the first grooveportion 182A and the third groove portion 182C in width and depth,damage to the proximal opening portion 92 due to friction can berestrained. In addition, since the groove portion 182 is covered withthe lid portion 183, the catheter shaft 20 can be restrained from flyingout of the groove portion 182, and the balloon 30 can be rotated in astable manner.

When the balloon catheter 10 is rotated, the balloon 30 may, in somecases, become eccentric due to bending along the axial direction X ofthe balloon 30. Since the dispensing tube 134 is flexible, however, evenif the balloon 30 becomes eccentric, the dispensing tube 134 moves aswell and follows the balloon 30, whereby good contact of these membersis maintained. Consequently, variations in the thickness of the coatingliquid applied can be restrained, and it becomes relatively easy tocontrol the thickness and the morphological form of the coating layer32.

Thereafter, the solvent contained in the coating liquid applied to thesurface of the balloon 30 is volatilized, and the coating layer 32containing the water-insoluble drug is formed on the surface of theballoon 30. The volatilization time is appropriately set according tothe solvent, and is, for example, approximately several seconds toseveral hundreds of seconds.

The amount of the drug contained in the coating layer 32 is notparticularly limited. The amount, in density, is 0.1 μg/mm² to 10μg/mm², preferably 0.5 μg/mm² to 5 μg/mm², more preferably 0.5 μg/mm² to4 μg/mm², and further preferably 1.0 μg/mm² to 3.5 μg/mm².

In addition, since the extending direction toward the ejection end 136of the dispensing tube 134 (ejection direction) is reverse to therotating direction of the balloon 30, the water-insoluble drug in thecoating layer 32 formed on the outer surface of the balloon 30 includesa morphological form wherein the crystals include a plurality ofelongate bodies having independent long axes.

The coating layer 32 having the morphological form wherein the crystalsinclude a plurality of elongate bodies having independent long axescontains the plurality of elongate bodies in the state of formingmutually independent elongate body shapes on the substrate (the outersurface of the balloon 30). The plurality of elongate bodies may extendsubstantially outward in the circumferential direction with respect tothe balloon surface, or may be arranged in directions substantiallyparallel to the circumferential direction. The plurality of elongatebodies may be present in the state of combination of these arrangements,or may be present in contact with each other such that the adjacentelongate bodies form different angles. The plurality of elongate bodiesmay be located with spaces (spaces not containing the crystal)therebetween on the balloon surface. Specifically, a preferable coatinglayer is a layer wherein a plurality of elongate bodies each composed ofthe crystal of the water-insoluble drug and having a long axis arepresent in a brush-like pattern. The plurality of elongate bodies arearranged in a circumferential and brush-like pattern on the surface ofthe substrate. Each of the elongate bodies is present independently, andhas a certain length, with one end (proximal end) of the length partbeing fixed to the substrate surface. The elongate body does not form acomposite structure, and is not interlocked, with the adjacent elongatebodies. The long axis of the crystal is substantially rectilinear. Theelongate body forms a predetermined angle with the substrate surfaceintersecting with the long axis thereof. The predetermined angle here isin the range of from 45 degrees to 135 degrees, preferably 70 degrees to110 degrees, and more preferably 80 degrees to 100 degrees. Furtherpreferably, the long axis of the elongate body forms an angle ofsubstantially 90 degrees with the substrate surface. The elongate body,at least its portion near the distal end thereof, is hollow. A sectionof the elongate body in a plane orthogonal to the long axis of theelongate body has a void (hollow portion). In the elongate body thushaving a void, the section of the elongate body in a plane orthogonal tothe long axis is polygonal in shape. The polygon here is, for example, atetragon, a pentagon, a hexagon or the like. Therefore, the elongatebody is formed as an elongate polyhedron that has a distal end (ordistal end surface) and a proximal end (or proximal end surface),wherein a side surface portion between the distal end (or distal endsurface) and the proximal end (or proximal end surface) is composed of aplurality of substantially plane surfaces. This crystallinemorphological form (hollow, elongate crystalline morphological form)constitutes the whole body or at least part of a plane surface on thesubstrate surface.

The layer having the morphological form including the hollow elongatecrystals is characterized as follows.

(1) A plurality of elongate bodies (rod-shaped bodies) havingindependent long axes, wherein the elongate bodies are hollow. Theelongate bodies are rod-like in shape (rod-shaped).

(2) The elongate bodies having long axes, wherein many of the elongatebodies are polyhedrons of which the section in a plane orthogonal to thelong axis is a polygon. Of the elongate crystals, not less than 50% byvolume are elongate polyhedrons. Side surfaces of the polyhedrons aremainly tetrahedron. In some cases, the elongate polyhedron has aplurality of surfaces (grooves) formed at a reentrant angle with avertex extending in the long axis direction. The reentrant angle heremeans that at least one of the internal angles of the polygon of thesection of the elongate body in a plane orthogonal to the long axis isan angle greater than 180 degrees.

(3) The elongate bodies having the long axes are elongate polyhedrons inmany cases. When viewed in a plane orthogonal to the long axis of theelongate body, the section of the elongate body is a polygon, which isobserved as a tetragon, a pentagon or a hexagon.

(4) The plurality of elongate bodies having independent long axes arealigned with the long axes at angles in a predetermined range,preferably in the range of from 45 degrees to 135 degrees, against thesubstrate surface. In other words, the plurality of elongate bodieshaving independent long axes stand together substantially uniformly onthe substrate surface. The region in which the elongate bodies standtogether extend in the circumferential direction and the axial directionof the substrate surface and is formed substantially uniformly. Theangles of the independent elongate bodies against the substrate surfacemay be different or the same within the predetermined range.

(5) Each of the elongate bodies having the independent long axes has itsone end (proximal end) of the length part thereof fixed to the substratesurface.

(6) The morphology of a part near the substrate surface, of the elongatebody, may in some cases be a stack of granular, short rod-shaped orshort curved line-shaped crystals. Some of the elongate bodies havingthe long axes have their long axes directly or indirectly on thesubstrate surface. Therefore, in some cases, the elongate bodies havingthe long axes stand together on the above-mentioned stack.

(7) The length of the elongate bodies having the long axes in the axialdirection is preferably 5 μm to 20 μm, more preferably 9 μm to 11 μm,and further preferably around 10 μm. The diameter of the elongate bodieshaving the long axes is preferably 0.01 μm to 5 μm, more preferably 0.05μm to 4 μm, and further preferably 0.1 μm to 3 μm.

(8) On the surface of the layer containing the hollow elongate bodycrystalline morphological form, there is no other morphological form(for example, an amorphous plate-shaped morphological form) mixed intherewith. Not less than 50% by volume, more preferably not less than70% by volume, of the crystals have the crystalline morphological formsof the above (1) to (7). Further preferably, substantially all thecrystals have the crystalline morphological form of the above (7).

(9) In the hollow elongate body crystalline morphological form, othercompound or compounds can be present in the coating layer containing thewater-insoluble drug constituting the crystals. In that case, the othercompound or compounds are present in the state of being distributed intospaces between the plurality of crystals (elongate bodies) of thewater-insoluble drug that stand together on the substrate surface of theballoon. As for the proportions of the substances constituting thecoating layer, in this case, the proportion (in percent by volume) ofthe crystals of the water-insoluble drug is by far greater than theproportion of the other compound or compounds.

(10) In the hollow elongate body crystalline morphological form, thewater-insoluble drug constituting the crystals exists on the substratesurface of the balloon. In the coating layer on the balloon substratesurface that has the water-insoluble drug constituting the crystals, nomatrix including the excipient is formed. Therefore, the water-insolubledrug constituting the crystals is not adhered in the matrix material.The water-insoluble drug constituting the crystals is even not embeddedin a matrix material.

(11) In the hollow elongate body crystalline morphological form, thecoating layer may contain crystal particles of the water-insoluble drugthat are regularly disposed on the substrate surface and excipientparticles of an excipient that are irregularly disposed between thecrystal particles. In this case, the molecular weight of the excipientis smaller than the molecular weight of the water-insoluble drug.Therefore, the proportion of the excipient particles per a predeterminedarea of the substrate is smaller than the proportion of the crystalparticles, and, accordingly, the excipient particles do not form amatrix. Here, the crystal particles of the water-insoluble drug may beone of the above-mentioned elongate bodies, the excipient particles arepresent in the state of being by far smaller than the crystal particlesof the water-insoluble drug and dispersed between the crystal particlesof the water-insoluble drug; accordingly, in some cases, the excipientparticles may not be observed in a scanning electron microscope (SEM)image or a laser microphotograph.

The crystal layer of the hollow elongate body morphological form, whendelivered into a living body as a coating layer formed by coating asubstrate surface of a medical device with the drug, is low in toxicityand high in stenosis inhibitory effect. The present inventors considerthat the reason for this lies in that the solubility of the drug havinga certain crystal morphology after transfer to tissue and the propertyfor being retained in the tissue have influences on these characteristicproperties. The water-insoluble drug including the hollow elongate bodycrystal morphology, upon transfer to the tissue, is reduced in the sizeof one unit of crystal; therefore, the drug is high in the property forpermeation into the tissue. In addition, the water-insoluble drug ishigh in solubility in the tissue. The high permeation property and highsolubility permit the drug to act effectively, whereby stenosis can beinhibited. The drug is considered to be low in toxicity because the drugis less liable to remain as large lumps in the tissue.

In addition, the layer including the hollow elongate body crystallinemorphological form is a morphological form wherein substantially uniformelongate bodies having long axes stand together substantially uniformlyand regularly on the substrate surface. Therefore, the size (the lengthin the long axis direction) of the crystals transferred to the tissue isas small as approximately 10 μm. For this reason, the drug actsuniformly on the lesion affected area, and its property for permeationinto the tissue is enhanced. Further, since the crystals transferred tothe tissue are small in size, a situation in which an excess amount ofthe drug would be retained in the lesion affected area for an excesstime is obviated. For this reason, the drug is considered to be able toshow a high stenosis inhibitory effect, without exhibiting toxicity.

Where the extending direction of the dispensing tube 134 or the ejectiondirection of the coating liquid is reverse to the rotating direction ofthe balloon 30, the water-insoluble drug in the coating layer 32acquires a morphological form including the hollow elongate bodycrystalline morphological form. The principle of this phenomenon may beconsidered to lie, for example, in that the coating liquid ejected fromthe ejection end 136 onto the balloon 30 is stimulated by the dispensingtube 134 due to the rotation. In addition, in the condition where a partof a side surface on the end portion side of the dispensing tube 134 (apart of the continuous length in the extending direction of thedispensing tube 134) is in contact with the outer surface of the balloon30, the coating liquid is ejected from the ejection end 136 onto theballoon 30. Consequently, appropriate contact can be realized betweenthe dispensing tube 134 and the balloon 30, such as to give themorphological form wherein the crystals of the water-insoluble druginclude a plurality of elongate bodies having independent long axes.

The coating liquid is ejected from the ejection end 136 onto the balloon30, in a region in which the balloon 30 is rotated toward the upper sidein the vertical direction. For this reason, the extending direction ofthe dispensing tube 134, which extends downward such as to ensure easyejection of the coating liquid, can be easily set to be reverse to therotating direction of the balloon 30.

If the material constituting the dispensing tube 134 coming into contactwith the balloon 30 is polyolefin (fluorine-free polyolefin) such aspolyethylene, polypropylene, etc., the dispensing tube 134 is lower inorganic solvent resistance but is higher in affinity for organicsolvents and smaller in contact angle with organic solvent, as comparedto a tube made of fluororesin such as PTFE. Accordingly, the coatingliquid is less liable to be repelled due to the characteristicproperties of the material of the dispensing tube 134 at the ejectionend 136 and at the part of contact with the balloon 30. Therefore,coating unevenness is less liable to occur in coating the outer surfaceof the balloon 30 with the coating liquid, and the uniformity of thecoating layer 32 can be controlled with high accuracy. Specifically,using a material not so high as fluororesin in organic solventresistance for the dispensing tube 134, it is possible to lower thepossibility of unevenness in coating the outer surface of the balloon 30with the coating liquid. In addition, where the material constitutingthe dispensing tube 134 is polyolefin such as polyethylene,polypropylene, etc., it is also possible to cause unevenness in coatingthe outer surface of the balloon 30 with the coating liquid, bycontrolling at least one of the moving speed of the dispensing tube 134,the ejection rate of the coating liquid, and the rotational speed of theballoon 30. For this reason, by forming the dispensing tube 134 frompolyolefin such as polyethylene or polypropylene, it is possible tofreely control the level of uniformity of the coating layer 32.

If the material constituting the dispensing tube 134 is fluororesin suchas PTFE, ETFE, PFA, FEP, etc., affinity for organic solvents is low andcontact angle with organic solvent is large. Accordingly, the coatingliquid is strongly repelled due to the characteristic properties of thematerial of the dispensing tube 134 at the ejection end 136 and at thecontact part with the balloon 30. Therefore, it is possible to easilycause unevenness (nonuniformity) in coating the outer surface of theballoon 30 with the coating liquid. Where the unevenness in coating withthe coating liquid is heavy, it is possible to increase the amount ofthe drug actually applied to some parts, while keeping constant thetotal amount of the drug contained in the coating layer 32 formed on theballoon 30. By this, it is possible to cause the drug to acteffectively, without increasing the burden on the living body. Theunevenness in coating is preferably a regular nonuniformity and ispreferably a stripe pattern (spiral linear body) in which linearlycoated parts are aligned in the axial direction X of the balloon 30. Byapplying the coating liquid while rotating the balloon 30 relative tothe dispensing tube 134, the coating layer 32 can be easily formed whileproducing unevenness of coating in a stripe pattern. Unevenness ofcoating is not restricted to the form of a stripe pattern; for example,a state where extremely shaded phases are formed may be adopted.

In the coating step, it is also possible to control the uniformity ofthe coating layer 32, by using both a dispensing tube 134 formed ofpolyolefin and another dispensing tube 134 formed of fluororesin andutilizing the aforementioned different characteristic properties of theresin materials. In the case of using both the dispensing tubes 134having the different characteristic properties, for example, at the timeof sequentially coating balloons 30 of a plurality of balloon catheters10, a control of changing the dispensing tube 134 according to theballoon 30 can be carried out. In addition, a control of changing thedispensing tube 134 depending on the part being coated of one balloon 30can also be performed.

The drug in the coating on the outer surface of the balloon 30 canassume different morphological forms such as crystalline form, amorphousform, and mixed forms thereof. In the case where the drug is of thecrystalline form, there exist various morphological forms which differin crystal structure. Further, crystals and amorphous phases may bedisposed regularly in the coating layer 32, or may be disposedirregularly in the coating layer 32.

With the dispensing tube 134 gradually moved in the axial direction X ofthe balloon 30 while rotating the balloon 30, the coating layer 32 isformed on the outer surface of the balloon 30 gradually along the axialdirection X. After the range of the part to be coated of the balloon 30is entirely formed thereon with the coating layer 32, the rotationdriving section 110, the tension section 150, the rectilinear movingsection 140 and the coating section 130 are stopped.

Thereafter, the balloon catheter 10 is dismounted from the ballooncoating apparatus 100, and the coating of the balloon 30 is completed.

As described above, the balloon coating method according to the firstembodiment is a balloon coating method for forming a coating layer 32containing a water-insoluble drug on an outer surface of a balloon 30 ofa balloon catheter 10, wherein the method includes: fitting a drivingshaft 111 for rotating the balloon catheter 10 to an opening portion ofa three-way cock 170 (interlock member) attached to a proximal portionof a hub 40 of the balloon catheter 10 and fixing the driving shaft 111in situ by a frictional force; and rotating the balloon 30 about theaxis X of the balloon 30 by the driving shaft 111 and applying a coatingliquid containing the drug to the outer surface of the balloon 30. Inthe balloon coating method configured as above, since the driving shaft111 is fitted and fixed to the opening portion formed in the three-waycock 170, the hub 40 is rotated about the center axis of the drivingshaft 111, and, therefore, the balloon 30 can be rotated while beingprevented as securely as possible from whirling. For this reason, theposition of the outer surface of the balloon 30 is not liable tofluctuate during rotation, and the coating liquid can be applied to theouter surface of the balloon 30 in an appropriate quantity. In addition,since the position of the outer surface of the balloon 30 is not liableto fluctuate during rotation, the contact force in contact of thedispensing tube 134 with the balloon 30 can be easily set to a desirablevalue, so that, for example, the morphological form of the drug in thecoating formed on the balloon 30 can be set appropriately. Note that theinterlock member is not limited to the three-way cock 170, and may, forexample, be a member produced for exclusive use.

In addition, since the driving shaft 111 is interlocked to the three-waycock 170 (interlock member) by a frictional force, the three-way cock170 is disengaged from the driving shaft 111 when a predeterminedtensile force is exerted thereon. Therefore, the three-way cock 170 isdisengaged from the driving shaft 111 before an excessive force acts onthe balloon 30 to damage the balloon 30; thus, damaging of the balloon30 can be inhibited.

According to the balloon coating method described above, in theapplication of the coating liquid, the coating liquid containing thedrug is applied to the outer surface of the balloon 30 while exerting onthe balloon 30 a tensile force pulling the balloon 30 in the axialdirection X of the balloon 30. As a result, any bend of the balloon 30is straightened by the tensile force, a rotating force transmitted fromthe hub 40 capable of stable rotation is stably transmitted to theballoon 30, whereby it can be ensured that the position of the outersurface of the balloon 30 is further less liable to fluctuate duringrotation. Therefore, the coating liquid can be applied to the outersurface of the balloon 30 in a more appropriate quantity. In addition,the contact force in contact of the dispensing tube 134 with the balloon30 can be easily set to a desirable value. Accordingly, for example, themorphological form of the drug in the coating formed on the balloon 30can be set more appropriately.

According to the balloon coating method described above, in the fixingof the proximal portion of the hub 40, the driving shaft 111 formed withthe male luer taper 116 having a shape according to the female luertaper 171 formed at the opening portion of the three-way cock 170(interlock member) is fitted and fixed to the female luer taper 171. Asa result, it is possible to position the three-way cock 170 relative tothe driving shaft 111 accurately and easily, to stabilize the rotation,and to ensure that the position of the outer surface of the balloon 30is not liable to fluctuate during rotation. In addition, by applyingmale luer tapers 116 prescribed by the standards to the driving shaft111, a variety of balloon catheters 10 produced adopting female luertapers 171 prescribed by the standards can be rotated by the drivingshaft 111.

Because the interlock member is a three-way cock 170, it is possible tointerlock the driving shaft 111 to the hub 40 through the three-way cock170, while ensuring that fluid can be caused to flow into and out of theballoon 30 through the three-way cock 170 by changing over a cockelement of the three-way cock 170.

Further, the balloon coating method according to the first embodiment isa balloon coating method for forming a coating layer 32 containing awater-insoluble drug on an outer surface of a balloon 30 of a ballooncatheter 10, wherein the method includes: inserting a core member 207into a guide wire lumen 91 penetrating the balloon 30, disposing aproximal portion of the core member 207 on the proximal side of aninflation region of the balloon 30 (a cylindrical portion 31 and taperedportions 33 on both sides thereof), with a distal portion of the coremember 207 protruding distally beyond a distal opening portion 93 of theguide wire lumen 91, and fixing by clamping together with the coremember 207 a part of the balloon catheter 10 that is on a distal side ofthe region of inflation of the balloon 30; and moving a dispensing tube134 for supplying a coating liquid containing the drug relative to theballoon 30 in an axial direction X of the balloon 30, while rotating theballoon 30 about the axis X of the balloon 30, to thereby apply thecoating liquid to the outer surface of the balloon 30. According to theballoon coating method configured as above, the distal portion of thecore member 207 protrudes distally beyond the distal opening portion 93of the guide wire lumen 91 and the part of the balloon catheter 10 thatis on the distal side of the region of inflation of the balloon 30 isfixed by clamping it together with the core member 207, and, therefore,deformation due to crushing of the balloon catheter 10 is inhibited fromoccurring at the time of the clamping. Further, since the proximalportion of the core member 207 is located on the proximal side of theinflation region of the balloon 30, the shape of the balloon 30 iseffectively straightened by the core member 207. Therefore, deformationand damaging of the balloon catheter 10 can be restrained. In addition,the position of the outer surface of the balloon 30 is not liable tofluctuate during rotation, and, accordingly, the coating liquid can beapplied to the outer surface of the balloon 30 in an appropriatequantity. In addition, since the position of the outer surface of theballoon 30 is not liable to fluctuate during rotation, the contact forcein contact of the dispensing tube 134 with the balloon 30 can be easilyset to a desirable value. Consequently, for example, the morphologicalform of the drug in the coating formed on the balloon 30 can be setappropriately.

In the balloon coating method as above, the balloon catheter 10 is of arapid exchange type. During the fixing of the balloon catheter 10, theballoon catheter 10 is fixed, with the proximal portion of the coremember 207 disposed on the distal side of the proximal opening portion92 of the guide wire lumen 91 without protruding from the proximalopening portion 92. This helps ensure that the core member 207 does notinterfere with surrounding members or the like when the balloon catheter10 is rotated, and that the position of the outer surface of the balloon30 is not liable to fluctuate during rotation. Therefore, the coatingliquid can be applied to the outer surface of the balloon 30 in a moreappropriate quantity. In addition, the contact force in contact of thedispensing tube 134 with the balloon 30 can be easily set to a desirablevalue, so that, for example, the morphological form of the drug in thecoating formed on the balloon 30 can be set more appropriately.

According to the balloon coating method as above, the position of theproximal portion of the core member 207 is coincident with the positionof the proximal end of the balloon 30 or is on the proximal side of theballoon 30, and the proximal portion of the core member 207 does notprotrude from the proximal opening portion 92. This makes it possible todispose the core member 207 at a position where the balloon 30 isprovided, while ensuring that the core member 207 does not protrude fromthe proximal opening portion 92 and the core member 207 is preventedfrom interfering with surrounding members or the like during rotation,whereby the rotation of the balloon 30 can be stabilized. Therefore, thecoating liquid can be applied to the outer surface of the balloon 30 ina more appropriate quantity. The contact force in contact of thedispensing tube 134 with the balloon 30 can be easily set to a desirablevalue, so that, for example, the morphological form of the drug in thecoating formed on the balloon 30 can be set more appropriately.

In the balloon coating method as above, the separated distance of theproximal portion of the core member 207 from the proximal openingportion 92 is up to 50 mm. This makes it possible to dispose the coremember 207 over a wide as possible range of the guide wire lumen 91,while ensuring that the core member 207 does not protrude from theproximal opening portion 92 and the core member 207 is prevented frominterfering with surrounding members or the like during rotation,whereby the rotation of the balloon 30 can be stabilized. Therefore, thecoating liquid can be applied to the outer surface of the balloon 30 ina more appropriate quantity. In addition, the contact force by which thedispensing tube 134 contacts the balloon 30 can be easily set to adesirable value, so that, for example, the morphological form of thedrug in the coating formed on the balloon 30 can be set moreappropriately.

In the balloon coating method as above, the value obtained bysubtracting the outside diameter of the core member 207 from the insidediameter of the guide wire lumen 91 is greater than 0 mm and not greaterthan 0.5 mm. Therefore, the diameter of the core member 207 is not toolarge in relation to the inside diameter of the guide wire lumen 91, sothat damage to the inner tube 90, in which is formed the guide wirelumen 91, by the core member 207 can be restrained effectively. Further,since the diameter of the core member 207 is not too small in relationto the inside diameter of the guide wire lumen 91, deformation of theinner tube 90 can be effectively restrained from occurring when theinner tube 90 is clamped.

Further, the balloon coating method according to the first embodiment isa balloon coating method for forming a coating layer 2 containing awater-insoluble drug on an outer surface of a balloon 30 of a ballooncatheter 10, wherein the method includes: fixing a distal joint portion34 (connection portion) between an inner tube 90 penetrating the insideof the balloon 30 and the balloon 30 in such a manner as to clamp thedistal joint portion 34 by at least two clamping portions 193 eachhaving a groove-shaped curved surface extending along the axis X of theinner tube 90; and moving a dispensing tube 134 for supplying a coatingliquid containing the drug relative to the balloon 30 in the axialdirection X of the balloon 30, while rotating the balloon 30 about theaxis of the balloon 30, to thereby apply the coating liquid to the outersurface of the balloon 30. According to the balloon coating methodconfigured as above, since the distal joint portion 34 constituting ajoint between the inner tube 90 and the balloon 30 is fixed in themanner of being clamped by the clamping portions 193 having thegroove-shaped curved surfaces, the inner tube 90 and the region ofinflation of the balloon 30 are prevented from being damaged, they canbe inhibited from becoming eccentric, and the position of the outersurface of the balloon 30 becomes less liable to fluctuate duringrotation. Therefore, the coating liquid can be applied to the outersurface of the balloon 30 in an appropriate quantity. In addition, sincethe position of the outer surface of the balloon 30 is less liable tofluctuate during rotation, the contact force in contact of thedispensing tube 134 with the balloon 30 can be easily set to a desirablevalue, so that, for example, the morphological form of the drug in thecoating formed on the balloon 30 can be set appropriately.

In addition, according to the balloon coating method as above, in theapplication of the coating liquid, the coating liquid containing thedrug is applied to the outer surface of the balloon 30 by rotating theballoon 30 while pulling the balloon 30 in the axial direction X of theballoon 30 by clamping portions 193. This ensures that bend of theballoon 30 is straightened by the tensile force, so that the position ofthe outer surface of the balloon 30 becomes less liable to fluctuateduring rotation. Therefore, the coating liquid can be applied to theouter surface of the balloon 30 in an appropriate quantity. In addition,the contact force in contact of the dispensing tube 134 with the balloon30 can be easily set to a desirable value, so that, for example, themorphological form of the drug in the coating formed on the balloon 30can be set more appropriately. Although a grasping force by the clampingportions 193 is increased because of the exertion of the tensile force,damaging of the inner tube 90 and the balloon 30 can be restrainedbecause the distal joint portion 34 is grasped by the clamping portions193 having the groove-shaped curved surfaces.

In the balloon coating method as above, at least two clamping portions193 are provided in a collet chuck 191. As a result, the distal jointportion 34 can be fixed by the collet chuck 191 easily and assuredly;further, a tensile force can be effectively exerted on the balloon 30.

Further, the balloon coating method according to the first embodiment isa balloon coating method for forming a coating layer 32 containing awater-insoluble drug on an outer surface of a balloon 30 of a ballooncatheter 10, wherein the method includes applying the coating liquidcontaining the drug to the outer surface of the balloon 30 by moving adispensing tube 134 for supplying the coating liquid relative to theballoon 30 in the axial direction X of the balloon 30, while rotatingthe balloon 30 about the axis X of the balloon 30 by applying rotatingforces to the balloon catheter 10 on both the proximal side and thedistal side of a region of inflation of the balloon 30 (a cylindricalportion 31 and tapered portions 33 on both sides thereof) and at thesame rotational speed. In the balloon coating method configured asabove, since the rotating forces are applied to the balloon catheter 10on both the proximal side and the distal side of the region of inflationof the balloon 30 and at the same rotational speed, the balloon 30becomes less liable to be twisted or to become eccentric. Therefore, theposition of the outer surface of the balloon 30 becomes less liable tofluctuate during rotation, so that the coating liquid can be applied tothe outer surface of the balloon 30 in an appropriate quantity. Inaddition, since the position of the outer surface of the balloon 30becomes less liable to fluctuate during rotation, the contact force incontact of the dispensing tube 134 with the balloon 30 can be easily setto a desirable value, so that, for example, the morphological form ofthe drug in the coating formed on the balloon 30 can be setappropriately.

According to the balloon coating method as above, in the step ofapplying the coating liquid, the coating liquid is applied to the outersurface of the balloon 30 by rotating the balloon 30 while pulling theballoon 30 in the axial direction X of the balloon 30. As a result,bending of the balloon catheter 10 is straightened by the tensile force,so that rotating forces can be easily applied to the balloon catheter 10from both the proximal portion and the distal portion of the ballooncatheter 10.

In addition, according to the balloon coating method as above, in theapplication of the coating liquid, the distal joint portion 34 betweenthe inner tube 90 penetrating the inside of the balloon 30 and theballoon 30 is clamped and pulled, whereby a tensile force is exerted inthe axial direction X of the balloon 30. As a result, a rotating forcecan be effectively applied to the balloon catheter 10 through the distaljoint portion 34, which is greater in thickness than the surroundingparts, has an outer circumferential surface composed of the flexiblematerial of the balloon 30, and is therefore easy to clamp and apply arotating force thereto.

According to the balloon coating method as above, in the step ofapplying the coating liquid, while the balloon 30 is being rotated aboutthe axis X of the balloon 30, an end portion of the flexible dispensingtube 134 that is formed with an opening portion for ejecting the coatingliquid contacts the outer surface of the balloon 30 in such a manner asto face in a direction reverse to the rotating direction of the balloon30. In this condition, the dispensing tube 134 is moved relative to theballoon 30 in the axial direction X of the balloon 30, and, concurrentlywith this movement, the coating liquid is ejected from the openingportion, whereby the coating liquid is applied to the outer surface ofthe balloon 30. As a result, the dispensing tube 134 facing in thedirection reverse to the rotating direction of the balloon 30 contactsthe balloon 30, whereby a frictional force there is increased, resultingin a condition where the balloon 30 might be liable to be twisted orbecome eccentric. When rotating forces are applied to the ballooncatheter 10 on both the proximal side and the distal side and at thesame rotational speed, however, the possibility of the balloon 30 beingtwisted or becoming eccentric can be lowered. Accordingly, rotation ofthe balloon 30 can be stabilized, while promoting crystallization of thewater-insoluble drug, by the dispensing tube 134 facing in the directionreverse to the rotating direction of the balloon 30. As a result, thecontact force in contact of the dispensing tube 134 with the balloon 30can be easily set to a desirable value, so that, for example, themorphological form of the drug in the coating formed on the balloon 30can be set appropriately.

Further, the balloon coating method according to the first embodiment isa balloon coating method for forming a coating layer 32 containing awater-insoluble drug on an outer surface of an inflatable balloon 30 ofa balloon catheter 10 having the balloon 30 at a distal portion of anelongate catheter shaft 20 (shaft), wherein the method includes:accommodating the catheter shaft 20 in a rectilinearly extending grooveportion 182 of a support base 181 provided with the groove portion 182,closing the groove portion 182 with a lid portion 183, and supportingthe catheter shaft 20 such that the catheter shaft 20 is rotatablewithin the groove portion 182; and moving a dispensing tube 134 forsupplying a coating liquid containing the drug relative to the balloon30 in the axial direction X of the balloon 30, while rotating theballoon 30 about the axis of the balloon 30, to thereby apply thecoating liquid to the outer surface of the balloon 30. In the ballooncoating method configured as above, since the catheter shaft 20 (shaft)of the balloon catheter 10 is rotated within the groove portion 182,bending of the catheter shaft 20 is straightened and an accurate rotarymotion is promoted, so that the balloon 30 becomes less liable to betwisted or become eccentric. Therefore, the position of the outersurface of the balloon 30 becomes less liable to fluctuate duringrotation, and the coating liquid can be applied to the outer surface ofthe balloon 30 in an appropriate quantity. In addition, since theposition of the outer surface of the balloon 30 becomes less liable tofluctuate during rotation, the contact force in contact of thedispensing tube 134 with the balloon 30 can be easily set to a desirablevalue, so that, for example, the morphological form of the drug in thecoating formed on the balloon 30 can be set appropriately. In addition,the catheter shaft 20 can be rotated while straightening its bend, byonly accommodating the catheter shaft 20 in the groove portion 182 andclosing the groove portion 182 with the lid portion 183, which ensuresan easy operation.

In the balloon coating method as above, the groove portion 182 islocated on an extension line of the driving shaft 111 for applying arotating force to the hub 40 of the balloon catheter 10. This helpsensure that the axis of the driving shaft 111 and the axis of thecatheter shaft 20 within the groove portion 182 coincide with eachother, so that rotation of the balloon catheter 10 is stabilized, andthe balloon 30 becomes less liable to be twisted or become eccentric.

In the balloon coating method as above, the groove portion 182 variesfrom part to part in at least one of width and depth. This enables thoseparts of the catheter shaft 20 which differ in shape or diameter to bedisposed in those parts of the groove portion 182 which differ in width,so that rotation of the catheter shaft 20 can be stabilized, whilerestraining abrasion or damaging of the catheter shaft 20.

According to the balloon coating method as above, in the application ofthe coating liquid, the balloon 30 is rotated by applying rotatingforces to the balloon catheter 10 on both the proximal side and thedistal side and at the same rotational speed. As a result, even in acondition where the rotation might become unstable due to a frictionalforce generated due to the rotation within the groove portion 182, theballoon 30 becomes less liable to be twisted or become eccentric, sincethe rotating forces are applied to the balloon catheter 10 on both theproximal side and the distal side and at the same rotational speed. Forthis reason, the position of the outer surface of the balloon 30 becomesless liable to fluctuate during rotation, so that the coating liquid canbe applied to the outer surface of the balloon 30 in an appropriatequantity. In addition, since the position of the outer surface of theballoon 30 becomes less liable to fluctuate during rotation, the contactforce in contact of the dispensing tube 134 with the balloon 30 can beeasily set to a desirable value, so that, for example, the morphologicalform of the drug in the coating formed on the balloon 30 can be setappropriately.

Because the coating liquid is ejected by putting the dispensing tube 134into contact with the outer surface of the balloon 30 in such a mannerthat the ejection end 136 faces in the direction reverse to the rotatingdirection of the balloon 30, the water-insoluble drug in the coatinglayer 32 formed on the outer surface of the balloon 30 can be set into amorphological form wherein the crystals of the drug include a pluralityof elongate bodies having independent long axes. In addition, in theballoon coating method as above, the coating liquid is ejected while thedispensing tube 134 is in contact with the outer surface of the balloon30 in such a manner that the ejection end 136 faces in the directionreverse to the rotating direction of the balloon 30, whereby anappropriate contact is realized between the dispensing tube 134 and theballoon 30, and, for example, the morphological form and the size of thedrug contained in the coating layer 32 can be set more freely.

Second Embodiment

A balloon coating method according to a second embodiment of the presentdisclosure includes rotating a balloon catheter 10 while holding theballoon catheter 10 on a support part rotatable together with theballoon catheter 10, thereby to form a coating layer 32 containing awater-insoluble drug on a surface of a balloon 30. The balloon coatingmethod according to the second embodiment is carried out by a ballooncoating apparatus 210 shown in FIGS. 11 and 12. The parts of theapparatus having the same or equivalent functions to those in the firstembodiment are denoted by the same reference symbols as used above, anda detailed description of these parts is not repeated.

The balloon coating apparatus 210 includes a rotation driving section220 (first rotation driving section) configured to apply a rotatingforce to the balloon catheter 10, a support part 230 configured tosupport the balloon catheter 10, and a bearing section 240 configured tosupport the support part 230 such that the support part 230 can berotated. Further, the balloon coating apparatus 210 includes a bed 121,a coating section 130 provided with a dispensing tube 134, a rectilinearmoving section 140 configured to move the dispensing tube 134, a tensionsection 150 (second rotation driving section), and a control unit 160configured to control the balloon coating apparatus 210.

The rotation driving section 220 includes a first motor 221 which isfixed to the bed 121 and holds the support part 230 such that thesupport part 230 can be rotated.

The support part 230 penetrates the first motor 221 and is supported tobe rotatable by the first motor 221. The support part 230 includes asupport base 231 for holding the balloon catheter 10, and a lid portion250 configured to clamp the balloon catheter 10 together with thesupport base 231. Further, the support part 230 includes hinge portions251 configured to interlock the lid portion 250 such that the lidportion 250 can be opened and closed relative to the bed 121, and asupport shaft 260 inserted in a three-way cock 170 attached to theballoon catheter 10.

The support base 231 includes a support base proximal portion 232penetrating the first motor 221, a support base distal portion 233 towhich the lid portion 250 is interlocked, and a support base centralportion 234 formed between the support base proximal portion 232 and thesupport base distal portion 233.

The support base proximal portion 232 is a part configured to support aproximal portion of the balloon catheter 10, and penetrates the firstmotor 221, with the support shaft 260 being fixed on the proximal sideof the first motor 221. The support shaft 260 is inserted in thethree-way cock 170 attached to the balloon catheter 10, and fixes aproximal portion of the balloon catheter 10. With the three-way cock 170attached to a hub 40, an inflation fluid can flow into the balloon 30 toinflate the balloon 30, by opening the three-way cock 170, and theinflated state of the balloon 30 can be maintained, by closing thethree-way cock 170.

The support base distal portion 233 is a part configured to support adistal portion of the catheter shaft 20, and is located on the distalside of the bearing section 240, with the lid portion 250 turnablyinterlocked by the hinge portions 251. The support base distal portion233 has a support surface 235 formed of a flexible material for clampingthe catheter shaft 20 between itself and the lid portion 250. Thesupport surface 235 is formed with a groove portion 236 in which part ofthe catheter shaft 20 is accommodated such that the catheter shaft 20can be clamped at an appropriate position. The lid portion 250 has apressing surface 252 formed of a flexible material for clamping thecatheter shaft 20 between itself and the support surface 235. Thesupport surface 235 and the pressing surface 252 are elasticallydeformed by clamping the catheter shaft 20 therebetween, and hold thecatheter shaft 20 by elastic forces. Examples of the material ormaterials constituting the support surface 235 and the pressing surface252 include expanded polyurethane and expanded polyethylene. The sidesurface of the support base distal portion 233 includes a recess 237configured to interlock with a locking mechanism 253 provided on the lidportion 250 for fixing the lid portion 250 to the support base distalportion 233. The locking mechanism 253 is, for example, snap fit.

The support base central portion 234 is formed with the support surface235 for supporting the catheter shaft 20, penetrates the bearing section240, and is rotatably supported by the bearing section 240.

The width and depth of the groove portion 236 are preferably smallerthan the outside diameter of the catheter shaft 20 by approximately 0.5mm to 3.5 mm, such that the catheter shaft 20 can be clamped between thegroove portion 236 and the lid portion 250.

The shape of the groove portion 236 in a section orthogonal to theX-direction has a semicircular bottom surface in this embodiment, thisis not restrictive; for example, the shape may be a V shape or atetragonal shape. The shape of the groove portion 236 is preferably sucha shape as to make surface contact with the catheter shaft 20, such thatthe catheter shaft 20 is not liable to be damaged. Therefore, the shapeof the groove portion 236 preferably does not have a projecting part,such as a W-shaped part, in section orthogonal to the X-direction. Thegroove portion 236 need not be provided.

The lid portion 250 is turnably held on the support base distal portion233 by the hinge portions 251, can cover the support surface 235 toclose the groove portion 236, and can be separated from the supportsurface 235 to expose the groove portion 236. The lid portion 250 isformed with the pressing surface 252 for clamping the catheter shaft 20against the support surface 235.

The balloon catheter 10 has a core member 207 disposed within a guidewire lumen 91. The core member 207 has its distal portion protrudingdistally beyond a distal opening portion 93 of the guide wire lumen 91,and has its proximal portion located on the proximal side of a positionof being clamped by the support surface 235 and the pressing surface252. The length of protrusion of the core member 207 from the distalopening portion 93 is not particularly limited. For restraining theballoon catheter 10 from being crushed when clamped by a collet chuck191, however, the protrusion length is preferably such a length as to beable to protrude assuredly, and is, for example, 2 mm to 50 mm.

Since the distal portion of the core member 207 protrudes distallybeyond the distal opening portion 93 of the guide wire lumen 91 and theproximal portion of the core member 207 is located on the proximal sideof the balloon 30, the core member 207 is present on the inside of thepart to be clamped by the clamping portions 193, whereby the ballooncatheter 10 can be restrained from deformation due to crushing.

Since the proximal portion of the core member 207 is located on theproximal side of the position of being clamped by the support base 231having the support surface 235 and the lid portion 250 having thepressing surface 252, the core member 207 is present on the inside ofthe part to be clamped by the support surface 235 and the pressingsurface 252, so that the balloon catheter 10 is restrained fromdeformation due to crushing.

The distal portion of the support shaft 260 is formed with a male luertaper 261 where its diameter decreases distally. The male luer taper261, by being inserted into a female luer taper 171 formed in thethree-way cock 170, can be fitted to the female luer taper 171 by africtional force. The taper ratio of the male luer taper 261 and thefemale luer taper 171 is prescribed in ISO 594 and JIS (commentary onstandards and reference concerning medical devices), and is prescribedto be 6%. The range of insertion of the support shaft 260 is within therange of the three-way cock 170. Therefore, the support shaft 260 can befitted to and detached from the three-way cock 170 easily, which ensuresenhanced usability.

The male luer taper 261 of the support shaft 260 may be inserted intoand fitted to the female luer taper 171 formed at a hub proximal openingportion 41 of the hub 40, instead of the three-way cock 170. The supportshaft 260 is not inserted distally beyond the hub 40. This permits thesupport shaft 260 to be fitted to and detached from the hub 40 easily,which ensures enhanced usability.

The control unit 160 is composed, for example, of a computer, andgenerally controls the rotation driving section 220, the rectilinearmoving section 140, the tension section 150 and the coating section 130.The control unit 160 can cause the first motor 221 of the rotationdriving section 220 and the second motor 154 of the tension section 150to rotate synchronously at the same rotational speed. In addition, thecontrol unit 160 can generally control the rotational speed of theballoon 30, initial positioning of the dispensing tube 134 relative tothe balloon 30, the moving speed of the dispensing tube 134 in the axialdirection X relative to the balloon 30, the ejection rate of the drugfrom the dispensing tube 134, and the like.

Now, a balloon coating method for forming a coating layer 32 containinga water-insoluble drug on a surface of a balloon 30 by use of theballoon coating apparatus 210 will be described below.

First, the three-way cock 170 is interlocked to the hub proximal openingportion 41 of the hub 40 of the balloon catheter 10, the three-way cock170 is opened, and an inflation fluid is introduced into the balloon 30by use of a syringe or the like to inflate the balloon 30, after whichthe three-way cock 170 is closed, to thereby maintain the inflated stateof the balloon 30. The coating layer 32 can also be formed on thesurface of the balloon 30 without inflating the balloon 30, and, in thatcase, it is unnecessary to supply an inflation fluid into the balloon30.

Next, the lid portion 250 interlocked to the support base 231 is opened,the catheter shaft 20 is accommodated in the groove portion 236, and thelid portion 250 is closed, such as to maintain a closed state by thelocking mechanism 253. As a result, the catheter shaft 20 is clamped andfixed between the support surface 235 and the pressing surface 252,while the support surface 235 and the pressing surface 252 which can beelastically deformed are deformed flexibly. In this instance,deformation of the catheter shaft 20 can be restrained, since the coremember 207 is inserted over the range of that part of the catheter shaft20 which is clamped between the support surface 235 and the pressingsurface 252.

Next, the male luer taper 261 of the support shaft 260 is inserted intoand interlocked to the female luer taper 171 of the three-way cock 170.By this, the hub 40 can be stably held by the support base 231 duringrotation. In addition, the catheter shaft 20 can also be fixed to thesupport base proximal portion 232 by a linear member 262, such as rubberband or wire.

Subsequently, a distal joint portion 34 of the balloon catheter 10 isclamped by the clamping portions 193 of the collet chuck 191. As aresult, a rotating force can be applied to a distal portion of theballoon catheter 10 from the second motor 154.

The order in which the balloon catheter 10 is disposed on the supportshaft 260, the collet chuck 191 and the support base 231 is notparticularly restricted.

Next, a dial 153 is rotated to move the second motor 154 and the colletchuck 191 distally, whereon a tensile force acts on the balloon catheter10, whereby bending of the balloon 30 is straightened. In this instance,since the catheter shaft 20 is clamped between the support surface 235and the pressing surface 252, the tensile force does not act on theproximal side of the part being clamped.

Subsequently, a driving portion 144 is operated, to position thedispensing tube 134 relative to the balloon 30. The dispensing tube 134is brought closer to an outer surface of the balloon 30, and is bent bybeing pressed against the balloon 30 when making contact with theballoon 30. In this instance, a side surface on an end portion side ofthe dispensing tube 134 is configured to contact the outer surface ofthe balloon 30, by appropriately disposing the relevant components.

Next, a coating liquid is supplied to the dispensing tube 134 whilecontrolling the liquid feed quantity by a liquid feed pump 132, and theballoon catheter 10 is rotated together with the support base 231 by thefirst motor 221 and the second motor 154. Then, a movable base 141 ismoved, to gradually move the dispensing tube 134 proximally along theX-direction. Since the dispensing tube 134 is moved relative to theballoon 30, the coating liquid ejected from an ejection end 136 of thedispensing tube 134 is applied to the outer surface of the balloon 30while drawing a spiral. That is, the coating liquid is applied to theouter surface of the balloon 30 in a spiral manner.

Since the balloon catheter 10 is clamped between the pressing surface252 and the support surface 235, the part on the proximal side of theposition of the part being clamped does not influence the rotation ofthe balloon 30. Therefore, stable rotation of the balloon 30 can berealized without strict restriction of bend, eccentricity or the like onthe proximal side of the position where the balloon catheter 10 isclamped between the pressing surface 252 and the support surface 235.Consequently, unevenness of the thickness of the coating liquid appliedcan be restrained, and it becomes easy to control the thickness andmorphological form of the coating layer 32.

Thereafter, the solvent contained in the coating liquid applied to thesurface of the balloon 30 is volatilized, resulting in the formation ofthe coating layer 32 containing the water-insoluble drug on the surfaceof the balloon 30.

Since the extending direction of the dispensing tube 134 toward theejection end 136 (the ejection direction) is reverse to the rotatingdirection of the balloon 30, the water-insoluble drug in the coatinglayer 32 formed on the outer surface of the balloon 30 is formed toinclude a morphological form wherein the crystals include a plurality ofelongate bodies having independent long axes.

The drug in the coating formed on the outer surface of the balloon 30can assume different morphological forms such as crystalline form,amorphous form and mixed forms thereof. Even where the drug assumes acrystalline form, there exist various morphological forms which differin crystal structure. Further, crystals and amorphous phases may bedisposed regularly in the coating layer 32, or may be disposedirregularly in the coating layer 32.

By moving the dispensing tube 134 gradually in the axial direction Xwhile rotating the balloon 30, the coating layer 32 is formed on theouter surface of the balloon 30 gradually along the axial direction X.After the range of the part to be coated of the balloon 30 is entirelycoated with the coating layer 32, the rotation driving section 220, therectilinear moving section 140, the tension section 150 and the coatingsection 130 are stopped.

Thereafter, the balloon catheter 10 is dismounted from the ballooncoating apparatus 210, and the coating of the balloon 30 is completed.

As aforementioned, the balloon coating method according to the secondembodiment is a balloon coating method for forming a coating layer 32containing a water-insoluble drug on an outer surface of an inflatableballoon 30 of a balloon catheter 10 having the balloon 30 provided at adistal portion of an elongate catheter shaft 20 (shaft), wherein themethod includes: holding the catheter shaft 20 on a support part 230rotatable about the axis X of the balloon 30; and moving a dispensingtube 134 for supplying the coating liquid containing the drug relativeto the balloon 30 in the axial direction X of the balloon 30, whilerotating the balloon 30 together with a support base 231, thereby toapply the coating liquid to the outer surface of the balloon 30.

In the balloon coating method configured as above, the balloon 30 isrotated in a state wherein the catheter shaft 20 is held on therotatable support part 230; therefore, bending of the catheter shaft 20and the like are not liable to influence the rotation of the balloon 30,so that the balloon 30 is not liable to be twisted or become eccentric.For this reason, the position of the outer surface of the balloon 30 isnot liable to fluctuate during rotation, so that the coating liquid canbe applied to the outer surface of the balloon 30 in an appropriatequantity. In addition, since the position of the outer surface of theballoon 30 is not liable to fluctuate during rotation, the contact forcein contact of the dispensing tube 134 with the balloon 30 can be easilyset to a desirable value, so that, for example, the morphological formof the drug in the coating formed on the balloon 30 can be setappropriately.

According to the balloon coating method as above, the support part 230includes the support base 231 formed with the rectilinear groove portion236 capable of accommodating at least part of the catheter shaft 20(shaft), and the lid portion 250 capable of covering the lid portion236, and, during the holding of the catheter shaft 20, the cathetershaft 20 is accommodated in the groove portion 236 and the grooveportion 236 is covered with the lid portion 250, to thereby hold thecatheter shaft 20 on the support part 230. As a result, the cathetershaft 20 can be held easily and assuredly in such a manner as not toslip off from the groove portion 236.

According to the balloon coating method as above, during the holding ofthe catheter shaft 20, the catheter shaft 20 is clamped by the supportbase 231 and the lid portion 250. Therefore, the catheter shaft 20 canbe firmly held on the support part 230, rotation of the balloon 30 isstabilized, and the balloon 30 becomes less liable to be twisted orbecome eccentric.

According to the balloon coating method as above, during the holding ofthe catheter shaft 20, the catheter shaft 20 is held by the support part230, with the core member 207 inserted in the catheter shaft 20. Thisensures that even when the catheter shaft 20 is held by the support part230, deformation of the catheter shaft 20 can be restrained.

According to the balloon coating method as above, while applying thecoating liquid, the balloon catheter 10 is rotatably supported by thebearing section 240, which is provided on the distal side of therotation driving section 220 for applying a rotating force to thesupport part 230, while rotating the balloon catheter 10 by the rotationdriving section 220. This results in that the rotation of the supportpart 230, which extends distally from the rotation driving section 220,is stabilized. Therefore, the rotation of the balloon 30 is stabilized,so that the balloon 30 becomes less liable to be twisted or geteccentric.

The present disclosure is not limited only to the aforementionedembodiments, and various modifications can be made by those skilled inthe art within the scope of the technical thought of the presentdisclosure. For example, while the coating liquid is applied to theballoon 30 from the distal side toward the proximal side of the balloon30 in the aforementioned first and second embodiments, the coatingliquid may be applied from the proximal side toward the distal side.

In addition, while the dispensing tube 134 extends downward along thevertical direction to contact the balloon 30 in the aforementioned firstand second embodiments, the extending direction of the dispensing tube134 is not specifically restricted. For instance, the extendingdirection may be inclined against the vertical direction, or thedispensing tube 134 may extend sideways or upward.

While the balloon catheter 10 whose balloon 30 is to be coated is arapid exchange type balloon catheter in the balloon coating methodsaccording to the aforementioned embodiments, a balloon of anover-the-wire type balloon catheter having a guide wire lumen from a hubto a distal portion may be coated.

Further, as in a modification of the first embodiment that isillustrated in FIG. 15, there may be provided a plurality of (in theexample shown in FIG. 15, two) support parts 270 by which the cathetershaft 20 is rotatably supported. The support parts 270 may bearbitrarily movable along the axis X of the balloon 30, or along theextending direction of groove portions (not shown) provided in thesupport parts 270. The plurality of support parts 270 are aligned alongthe extending direction of the groove portions (not shown) provided inthe support parts 270.

With the catheter shaft 20 thus supported by the plurality of supportparts 270, the rotation of the elongate catheter shaft 20 can bestabilized, while reducing the friction between each support part 270and the catheter shaft 20 and thereby restraining abrasion or damagingof the catheter shaft 20.

In addition, since the support parts 270 are movable, the support parts270 can be moved prior to the step of supporting the catheter shaft 20by the support parts 270. As a result, the catheter shaft 20 can besupported at desirable positions, whereby rotation of the ballooncatheter 10 can be stabilized.

Each support base may be provided with a plurality of lid portions.

Having described several embodiments of the present disclosure whichrepresent examples of the balloon coating method and balloon rotatingmethod disclosed here, it is to be understood that the disclosure is notlimited to those precise embodiments and that various changes andmodifications could be effected therein by those skilled in the artwithout departing from the spirit or scope of the disclosure as definedin the appended claims. It is expressly intended that all such changes,modifications and equivalents which fall within the scope of the claimsare embraced by the claims.

What is claimed is:
 1. A balloon coating method for forming a coatinglayer containing a water-insoluble drug on an outer surface of a balloonof a balloon catheter, the balloon coating method comprising: fixing aconnection portion between the balloon and an inner tube passing throughan inside of the balloon by clamping the connection portion with atleast two clamping portions each including a groove-shaped curvedsurface extending along an axis of the inner tube; pulling the balloonin an axial direction of the balloon by the clamping portions to therebystraighten a bend of the balloon; and moving a dispensing tube relativeto the balloon in an axial direction of the balloon while rotating theballoon about an axis of the balloon and while also dispensing thecoating liquid containing the water-insoluble drug from the dispensingtube to apply the coating liquid to the outer surface of the balloon. 2.The balloon coating method according to claim 1, further comprisingrotating the balloon while, dispensing the coating liquid from thedispensing tube and while pulling the balloon in the axial direction ofthe balloon by the clamping portions.
 3. The balloon coating methodaccording to claim 1, wherein the at least two clamping portions areprovided in a collet chuck.
 4. The balloon coating method according toclaim 1, wherein each of the at least two clamping portions possesses atapered outer surface, the at least two clamping portions beingpositioned in a holder possessing a tapered inner surface, and theclamping of the connection portion with the at least two clampingportions comprising relatively moving the holder and the at least twoclamping portions so that the tapered outer surfaces of the at least twoclamping portions contact and move along the tapered inner surface ofthe holder to cause the at least two clamping portions to move inwardlytowards the connection portion.
 5. The balloon coating method accordingto claim 1, wherein the at least two clamping portions are connected toa motor, the pulling of the balloon in the axial direction of theballoon comprising axially moving the motor.
 6. The balloon coatingmethod according to claim 5, wherein the rotating of the balloon aboutthe axis of the balloon includes rotating the at least two clampingportions through operation of the motor.
 7. The balloon coating methodaccording to claim 1, wherein the at least two clamping portions areconnected to a motor, and the rotating of the balloon about the axis ofthe balloon includes rotating the at least two clamping portions throughoperation of the motor.
 8. A balloon rotating method for rotating aballoon catheter that includes a balloon possessing an axis and an innertube passing through the balloon, the balloon possessing one end portionaxially overlapping and connected in a fluid-tight manner to the innertube at a connection portion, the balloon rotating method comprising:clamping the connection portion by at least two clamping portions eachincluding a groove-shaped curved surface extending along the axis of theinner tube; and rotating the balloon about the axis of the balloon whilethe connection portion is clamped by the clamping portions.
 9. Theballoon rotating method according to claim 8, further comprising pullingthe balloon in an axial direction of the balloon by the clampingportions.
 10. The balloon rotating method according to claim 8, whereinthe at least two clamping portions are part of a collet chuck.
 11. Theballoon rotating method according to claim 8, wherein each of the atleast two clamping portions possesses a tapered outer surface, the atleast two clamping portions being positioned in a holder possessing atapered inner surface, and the clamping of the connection portion withthe at least two clamping portions comprising relatively moving theholder and the at least two clamping portions so that the tapered outersurfaces of the at least two clamping portions contact and move alongthe tapered inner surface of the holder to cause the at least twoclamping portions to move inwardly towards the connection portion. 12.The balloon rotating method according to claim 8, wherein the at leasttwo clamping portions are connected to a motor, the rotating of theballoon comprising rotating the balloon through operation of the motor.13. The balloon rotating method according to claim 12, furthercomprising pulling the balloon in an axial direction of the balloon byaxially moving the motor.
 14. A balloon coating apparatus configured toform a coating layer containing a water-insoluble drug on an outersurface of a balloon of a balloon catheter, the balloon coatingapparatus comprising: at least two clamping portions configured to fix,by way of clamping, a connection portion between the balloon and aninner tube penetrating an inside of the balloon, the clamping portionseach including a groove-shaped curved surface extending along an axis ofthe inner tube; a rotation driving section configured to rotate theballoon catheter; and a coating section that moves a dispensing tube,configured to dispense the coating liquid containing the drug, relativeto the balloon in an axial direction of the balloon to thereby coat theouter surface of the balloon with the coating liquid.
 15. The ballooncoating apparatus according to claim 14, further comprising: a tensionsection that applies a tensile force for pulling the balloon in theaxial direction of the balloon while allowing the balloon to rotate. 16.The balloon coating apparatus according to claim 14, wherein the atleast two clamping portions are part of a collet chuck.
 17. The ballooncoating apparatus according to claim 14, wherein each of the at leasttwo clamping portions possesses a tapered outer surface, the at leasttwo clamping portions being positioned in a holder possessing a taperedinner surface that is contacted by the tapered outer surfaces of the atleast two clamping portions as the at least two clamping portions aremoved axially to move the at least two clamping portions inwardlytowards the connection portion.
 18. The balloon coating apparatusaccording to claim 14, wherein the rotation driving section includes amotor connected to the at least two clamping portions so that operationof the motor results in rotation of the at least two clamping portions.19. The balloon coating apparatus according to claim 18, wherein themotor is one motor, and the rotation driving section including anothermotor connectable to a proximal end of the catheter balloon.
 20. Theballoon coating apparatus according to claim 18, wherein the motor isaxially movably mounted on a base section to apply tension to theballoon by axially moving the motor away from the balloon catheter.